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Synthetic amorphous silica nanoparticles: toxicity, biomedical and environmental implications

Nature Reviews Materials volume 5, pages 886–909 (2020)Cite this article

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Abstract

Natural silica and silicates are predominantly crystalline and constitute the most abundant components of the Earth’s crust. Man-made silica is typically amorphous and manufactured in tonnage quantities for commercial use and, more recently, for burgeoning medical applications, making synthetic amorphous silica nanoparticles (SASNs) arguably the most abundant nanoparticles on Earth. Despite the abundance of silica and SASNs, misconceptions remain regarding what silica is and its medical and environmental implications. SASNs are often considered to be toxic regardless of their source, but, here, we emphasize that all silica nanoparticles are not created equal and explore how composition, synthesis, processing and environmental exposure effect toxicity. Despite having comparable size, shape and nominal composition, SASNs prepared by pyrolytic or colloidal processes can have drastically different toxicities, which, to date, is not generally recognized by the research community. In this Review, we begin with a survey of relationships between synthetic methods and material structure, followed by structure–toxicity relationships. Next, we explore the environmental implications of SASNs exposure and provide a review of the emerging biomedical uses of SASNs in therapy, imaging and theranostics. We conclude with our vision for the field and suggest that minimal SASN characterization standards are needed for reporting and understanding their biological or environmental behaviours and implications.

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Fig. 1: The framework and surface chemistry of amorphous and crystalline silica.
Fig. 2: Timeline of the development and taxonomy of synthetic amorphous silica nanoparticles.
Fig. 3: Synthesis–structure–biosafety relationships of fumed and colloidal silicas.
Fig. 4: Representative data sets of physicochemical determinants of the toxicity of synthetic amorphous silica nanoparticles.
Fig. 5: Cell viability and haemolytic behaviour of various silica nanoparticles.
Fig. 6: Intracellular fate of silica nanoparticles.
Fig. 7: Select surface modifications of synthetic amorphous silica nanoparticles and their functions.
Fig. 8: Schematic of in vivo toxicology testing.
Fig. 9: Relationships between the six main sources of silica on Earth.
Fig. 10: A schematic of the modular features of mesoporous silica and silsesquioxane-based delivery platforms.
Fig. 11: A selection of mesoporous silica supramolecular nanovalves and nanomachines developed to achieve stimulus-triggered release of cargo.

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References

  1. Haynes, W. M., Lide, D. R. & Bruno, T. J. Abundance of Elements in the Earth’s Crust and in the Sea (CRC, 2016–2017).

  2. Heaney, P. J. Structure and chemistry of the low-pressure silica polymorphs. Rev. Mineral. Geochem. 29, 1–40 (1994).

    CAS  Google Scholar 

  3. Iler, R. K. The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties and Biochemistry of Silica (Wiley, 1979).

  4. Pratsinis, S. E. Flame aerosol synthesis of ceramic powders. Prog. Energy Combust. Sci. 24, 197–219 (1998).

    CAS  Google Scholar 

  5. Ibaseta, N. & Biscans, B. Fractal dimension of fumed silica: comparison of light scattering and electron microscope methods. Powder Technol. 203, 206–210 (2010).

    CAS  Google Scholar 

  6. Zhang, H. et al. Processing pathway dependence of amorphous silica nanoparticle toxicity: colloidal vs pyrolytic. J. Am. Chem. Soc. 134, 15790–15804 (2012).

    CAS  Google Scholar 

  7. AEROSIL® - Fumed Silica Technical Overview (Evonik Industries, 2015).

  8. Argyo, C., Weiss, V., Bräuchle, C. & Bein, T. Multifunctional mesoporous silica nanoparticles as a universal platform for drug delivery. Chem. Mater. 26, 435–451 (2014).

    CAS  Google Scholar 

  9. Sun, B., Zhou, G. & Zhang, H. Synthesis, functionalization, and applications of morphology-controllable silica-based nanostructures: a review. Prog. Solid State Chem. 44, 1–19 (2016).

    Google Scholar 

  10. Tang, L. & Cheng, J. Nonporous silica nanoparticles for nanomedicine application. Nano Today 8, 290–312 (2013).

    CAS  Google Scholar 

  11. Yamamoto, E. & Kuroda, K. Colloidal mesoporous silica nanoparticles. Bull. Chem. Soc. Jpn. 89, 501–539 (2016).

    CAS  Google Scholar 

  12. Mebert, A. M., Baglole, C. J., Desimone, M. F. & Maysinger, D. Nanoengineered silica: properties, applications and toxicity. Food Chem. Toxicol. 109, 753–770 (2017).

    CAS  Google Scholar 

  13. Pfeiffer-Laplaud, M., Costa, D., Tielens, F., Gaigeot, M.-P. & Sulpizi, M. Bimodal acidity at the amorphous silica/water interface. J. Phys. Chem. C 119, 27354–27362 (2015).

    CAS  Google Scholar 

  14. Brinker, C. J. & Scherer, G. W. Sol-Gel Science: The Physics and Chemistry of Sol-Gel Processing (Academic, 2013).

  15. Stöber, W., Fink, A. & Bohn, E. Controlled growth of monodisperse silica spheres in the micron size range. J. Colloid Interface Sci. 26, 62–69 (1968).

    Google Scholar 

  16. Yang, P., Gai, S. & Lin, J. Functionalized mesoporous silica materials for controlled drug delivery. Chem. Soc. Rev. 41, 3679–3698 (2012).

    CAS  Google Scholar 

  17. Croissant, J. G., Fatieiev, Y., Almalik, A. & Khashab, N. M. Mesoporous silica and organosilica nanoparticles: physical chemistry, biosafety, delivery strategies, and biomedical applications. Adv. Healthc. Mater. 7, 1700831 (2018).

    Google Scholar 

  18. Raman, N. K., Anderson, M. T. & Brinker, C. J. Template-based approaches to the preparation of amorphous, nanoporous silicas. Chem. Mater. 8, 1682–1701 (1996).

    CAS  Google Scholar 

  19. Biegler, H. & Kallrath, G. Process for producing silica in the form of hollow spheres. US Patent US3,383,172A (1968).

  20. Yanagisawa, T., Shimizu, T., Kuroda, K. & Kato, C. The preparation of alkyltriinethylaininonium–kaneinite complexes and their conversion to microporous materials. Bull. Chem. Soc. Jpn. 63, 988–992 (1990).

    CAS  Google Scholar 

  21. Beck, J. S. et al. A new family of mesoporous molecular-sieves prepared with liquid-crystal templates. J. Am. Chem. Soc. 114, 10834–10843 (1992).

    CAS  Google Scholar 

  22. Zhao, D. et al. Triblock copolymer syntheses of mesoporous silica with periodic 50 to 300 angstrom pores. Science 279, 548–552 (1998).

    CAS  Google Scholar 

  23. Lu, Y. et al. Aerosol-assisted self-assembly of mesostructured spherical nanoparticles. Nature 398, 223–226 (1999).

    CAS  Google Scholar 

  24. Lai, C.-Y. et al. A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules. J. Am. Chem. Soc. 125, 4451–4459 (2003).

    CAS  Google Scholar 

  25. Castillo, R. R. et al. Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update. Expert Opin. Drug Deliv. 16, 415–439 (2019).

    CAS  Google Scholar 

  26. Wang, Y. et al. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomedicine 11, 313–327 (2015).

    CAS  Google Scholar 

  27. Wen, J. et al. Diverse gatekeepers for mesoporous silica nanoparticle based drug delivery systems. Chem. Soc. Rev. 46, 6024–6045 (2017).

    CAS  Google Scholar 

  28. Croissant, J. & Zink, J. I. Nanovalve-controlled cargo release activated by plasmonic heating. J. Am. Chem. Soc. 134, 7628–7631 (2012).

    CAS  Google Scholar 

  29. Liong, M., France, B., Bradley, K. A. & Zink, J. I. Antimicrobial activity of silver nanocrystals encapsulated in mesoporous silica nanoparticles. Adv. Mater. 21, 1684–1689 (2009).

    CAS  Google Scholar 

  30. Dib, S. et al. Versatile heavy metals removal via magnetic mesoporous nanocontainers. RSC Adv. 4, 24838–24841 (2014).

    CAS  Google Scholar 

  31. Thomas, C. R. et al. Noninvasive remote-controlled release of drug molecules in vitro using magnetic actuation of mechanized nanoparticles. J. Am. Chem. Soc. 132, 10623–10625 (2010).

    CAS  Google Scholar 

  32. Niu, N. et al. Up-conversion nanoparticle assembled mesoporous silica composites: synthesis, plasmon-enhanced luminescence, and near-infrared light triggered drug release. ACS Appl. Mater. Interfaces 6, 3250–3262 (2014).

    CAS  Google Scholar 

  33. Dong, J. & Zink, J. I. Light or heat? The origin of cargo release from nanoimpeller particles containing upconversion nanocrystals under IR irradiation. Small 11, 4165–4172 (2015).

    CAS  Google Scholar 

  34. Cauda, V., Argyo, C. & Bein, T. Impact of different PEGylation patterns on the long-term bio-stability of colloidal mesoporous silica nanoparticles. J. Mater. Chem. 20, 8693–8699 (2010).

    CAS  Google Scholar 

  35. Yao, V. J. et al. Ligand-targeted theranostic nanomedicines against cancer. J. Control. Release 240, 267–286 (2016).

    CAS  Google Scholar 

  36. Meng, H. et al. Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice. ACS Nano 9, 3540–3557 (2015).

    CAS  Google Scholar 

  37. Cauda, V. et al. Colchicine-loaded lipid bilayer-coated 50 nm mesoporous nanoparticles efficiently induce microtubule depolymerization upon cell uptake. Nano Lett. 10, 2484–2492 (2010).

    CAS  Google Scholar 

  38. Ambrogio, M. W., Thomas, C. R., Zhao, Y.-L., Zink, J. I. & Stoddart, J. F. Mechanized silica nanoparticles: a new frontier in theranostic nanomedicine. Acc. Chem. Res. 44, 903–913 (2011).

    CAS  Google Scholar 

  39. Lu, J., Choi, E., Tamanoi, F. & Zink, J. I. Light-activated nanoimpeller-controlled drug release in cancer cells. Small 4, 421–426 (2008).

    CAS  Google Scholar 

  40. Angelos, S. et al. pH clock-operated mechanized nanoparticles. J. Am. Chem. Soc. 131, 12912–12914 (2009).

    CAS  Google Scholar 

  41. Croissant, J. et al. Two-photon-triggered drug delivery via fluorescent nanovalves. Small 10, 1752–1755 (2014).

    CAS  Google Scholar 

  42. Mizoshita, N., Tani, T. & Inagaki, S. Syntheses, properties and applications of periodic mesoporous organosilicas prepared from bridged organosilane precursors. Chem. Soc. Rev. 40, 789–800 (2011).

    CAS  Google Scholar 

  43. Inagaki, S., Guan, S., Ohsuna, T. & Terasaki, O. An ordered mesoporous organosilica hybrid material with a crystal-like wall structure. Nature 416, 304–307 (2002).

    CAS  Google Scholar 

  44. Fatieiev, Y., Croissant, J., Alamoudi, K. & Khashab, N. Cellular internalization and biocompatibility of periodic mesoporous organosilica nanoparticles with tunable morphologies: from nanospheres to nanowires. ChemPlusChem 82, 631–637 (2017).

    CAS  Google Scholar 

  45. Jimenez, C. M. et al. Nanodiamond-PMO for two-photon PDT and drug delivery. J. Mater. Chem. B 4, 5803–5808 (2016).

    CAS  Google Scholar 

  46. Croissant, J. G., Cattoën, X., Wong Chi Man, M., Durand, J. O. & Khashab, N. M. Syntheses and applications of periodic mesoporous organosilica nanoparticles. Nanoscale 7, 20318–20334 (2015).

    CAS  Google Scholar 

  47. Aggad, D. et al. Gemcitabine delivery and photodynamic therapy in cancer cells via porphyrin-ethylene-based periodic mesoporous organosilica nanoparticles. ChemNanoMat 4, 46–51 (2018).

    CAS  Google Scholar 

  48. Croissant, J. G. et al. Fluorescent periodic mesoporous organosilica nanoparticles dual-functionalized via click chemistry for two-photon photodynamic therapy in cells. J. Mater. Chem. B 4, 5567–5574 (2016).

    CAS  Google Scholar 

  49. Croissant, J. et al. Biodegradable oxamide-phenylene-based mesoporous organosilica nanoparticles with unprecedented drug payloads for delivery in cells. Chem. Eur. J. 22, 14806–14811 (2016).

    CAS  Google Scholar 

  50. Urata, C. et al. Aqueous colloidal mesoporous nanoparticles with ethenylene-bridged silsesquioxane frameworks. J. Am. Chem. Soc. 133, 8102–8105 (2011).

    CAS  Google Scholar 

  51. Auras, F. et al. A zinc phthalocyanine based periodic mesoporous organosilica exhibiting charge transfer to fullerenes. Chem. Eur. J. 20, 14971–14975 (2014).

    CAS  Google Scholar 

  52. Jimenez, C. M. et al. Porous porphyrin-based organosilica nanoparticles for NIR two-photon photodynamic therapy and gene delivery in zebrafish. Adv. Funct. Mater. 28, 1800235 (2018).

    Google Scholar 

  53. Pavan, C. et al. In search of the chemical basis of the hemolytic potential of silicas. Chem. Res. Toxicol. 26, 1188–1198 (2013).

    CAS  Google Scholar 

  54. Vallyathan, V., Shi, X. & Castranova, V. Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis. Environ. Health Perspect. 106, 1151–1155 (1998).

    CAS  Google Scholar 

  55. Brinker, C. J., Kirkpatrick, R. J., Tallant, D. R., Bunker, B. C. & Montez, B. NMR confirmation of strained “defects” in amorphous silica. J. Non-Cryst. Solids 99, 418–428 (1988).

    CAS  Google Scholar 

  56. Fatieiev, Y. et al. Photoresponsive bridged silsesquioxane nanoparticles with tunable morphology for light-triggered plasmid DNA delivery. ACS Appl. Mater. Interfaces 7, 24993–24997 (2015).

    CAS  Google Scholar 

  57. Croissant, J. G., Cattoën, X., Durand, J.-O., Man, M. W. C. & Khashab, N. M. Organosilica hybrid nanomaterials with a high organic content: syntheses and applications of silsesquioxanes. Nanoscale 8, 19945–19972 (2016).

    CAS  Google Scholar 

  58. Inagaki, S. et al. Light harvesting by a periodic mesoporous organosilica chromophore. Angew. Chem. Int. Ed. 48, 4042–4046 (2009).

    CAS  Google Scholar 

  59. Vu, B. T. et al. Chick chorioallantoic membrane assay as an in vivo model to study the effect of nanoparticle-based anticancer drugs in ovarian cancer. Sci. Rep. 8, 8524 (2018).

    Google Scholar 

  60. Hammami, M. A. et al. Engineering hydrophobic organosilica nanoparticle-doped nanofibers for enhanced and fouling resistant membrane distillation. ACS Appl. Mater. Interfaces 9, 1737–1745 (2017).

    CAS  Google Scholar 

  61. Croissant, J. G., Fatieiev, Y. & Khashab, N. M. Degradability and clearance of silicon, organosilica, silsesquioxane, silica mixed oxide, and mesoporous silica nanoparticles. Adv. Mater. 29, 1604634 (2017).

    Google Scholar 

  62. Braun, K. et al. Dissolution kinetics of mesoporous silica nanoparticles in different simulated body fluids. J. Sol-Gel Sci. Technol. 79, 319–327 (2016).

    CAS  Google Scholar 

  63. Möller, K. & Bein, T. Degradable drug carriers: vanishing mesoporous silica nanoparticles. Chem. Mater. 31, 4364–4378 (2019).

    Google Scholar 

  64. Fatieiev, Y. et al. Enzymatically degradable hybrid organic–inorganic bridged silsesquioxane nanoparticles for in vitro imaging. Nanoscale 7, 15046–15050 (2015).

    CAS  Google Scholar 

  65. Croissant, J. et al. Biodegradable ethylene-bis(propyl)disulfide-based periodic mesoporous organosilica nanorods and nanospheres for efficient in-vitro drug delivery. Adv. Mater. 26, 6174–6180 (2014).

    CAS  Google Scholar 

  66. Huang, P. et al. Metalloporphyrin-encapsulated biodegradable nanosystems for highly efficient magnetic resonance imaging-guided sonodynamic cancer therapy. J. Am. Chem. Soc. 139, 1275–1284 (2017).

    CAS  Google Scholar 

  67. Omar, H. et al. Biodegradable magnetic silica@iron oxide nanovectors with ultra-large mesopores for high protein loading, magnetothermal release, and delivery. J. Control. Release 259, 187–194 (2016).

    Google Scholar 

  68. He, Y., Zeng, B., Liang, S., Long, M. & Xu, H. Synthesis of pH-responsive biodegradable mesoporous silica–calcium phosphate hybrid nanoparticles as a high potential drug carrier. ACS Appl. Mater. Interfaces 9, 44402–44409 (2017).

    CAS  Google Scholar 

  69. Wang, L., Huo, M., Chen, Y. & Shi, J. Coordination-accelerated “iron extraction” enables fast biodegradation of mesoporous silica-based hollow nanoparticles. Adv. Healthc. Mater. 6, 1700720 (2017).

    Google Scholar 

  70. Yu, L. et al. “Manganese extraction” strategy enables tumor-sensitive biodegradability and theranostics of nanoparticles. J. Am. Chem. Soc. 138, 9881–9894 (2016).

    CAS  Google Scholar 

  71. Tsyganenko, A. et al. Brønsted acidity of silica silanol groups induced by adsorption of acids. Catal. Lett. 70, 159–163 (2000).

    CAS  Google Scholar 

  72. Pavan, C. et al. Ζ potential evidences silanol heterogeneity induced by metal contaminants at the quartz surface: implications in membrane damage. Colloids Surf. B Biointerfaces 157, 449–455 (2017).

    CAS  Google Scholar 

  73. Turci, F. et al. Revisiting the paradigm of silica pathogenicity with synthetic quartz crystals: the role of crystallinity and surface disorder. Part. Fibre Toxicol. 13, 32 (2016).

    Google Scholar 

  74. Zhuravlev, L. The surface chemistry of amorphous silica. Zhuravlev model. Colloids Surf. A Physicochem. Eng. Asp. 173, 1–38 (2000).

    CAS  Google Scholar 

  75. Yu, T., Hubbard, D., Ray, A. & Ghanderhari, H. In vivo biodistribution and pharmacokinetics of silica nanoparticles as a function of geometry, porosity and surface characteristics. J. Control. Release 163, 46–54 (2012).

    CAS  Google Scholar 

  76. He, Q., Zhang, Z., Gao, Y., Shi, J. & Li, Y. Intracellular localization and cytotoxicity of spherical mesoporous silica nano- and microparticles. Small 5, 2722–2729 (2009).

    CAS  Google Scholar 

  77. Croissant, J. et al. Mixed periodic mesoporous organosilica nanoparticles and core–shell systems, application to in vitro two-photon imaging, therapy, and drug delivery. Chem. Mater. 26, 7214–7220 (2014).

    CAS  Google Scholar 

  78. Chen, L. et al. The toxicity of silica nanoparticles to the immune system. Nanomedicine 13, 1939–1962 (2018).

    Google Scholar 

  79. Hsiao, I. L. et al. Biocompatibility of amine-functionalized silica nanoparticles: the role of surface coverage. Small 15, 1805400 (2019).

    Google Scholar 

  80. Guo, C. et al. Mitochondrial dysfunction, perturbations of mitochondrial dynamics and biogenesis involved in endothelial injury induced by silica nanoparticles. Environ. Pollut. 236, 926–936 (2018).

    CAS  Google Scholar 

  81. Murugadoss, S. et al. Toxicology of silica nanoparticles: an update. Arch. Toxicol. 91, 2967–3010 (2017).

    CAS  Google Scholar 

  82. Pavan, C. & Fubini, B. Unveiling the variability of “quartz hazard” in light of recent toxicological findings. Chem. Res. Toxicol. 30, 469–485 (2016).

    Google Scholar 

  83. Kim, I.-Y., Joachim, E., Choi, H. & Kim, K. Toxicity of silica nanoparticles depends on size, dose, and cell type. Nanomedicine 11, 1407–1416 (2015).

    CAS  Google Scholar 

  84. Spyrogianni, A., Herrmann, I. K., Keevend, K., Pratsinis, S. E. & Wegner, K. The silanol content and in vitro cytolytic activity of flame-made silica. J. Colloid Interface Sci. 507, 95–106 (2017).

    CAS  Google Scholar 

  85. Pavan, C., Rabolli, V., Tomatis, M., Fubini, B. & Lison, D. Why does the hemolytic activity of silica predict its pro-inflammatory activity? Part. Fibre Toxicol. 11, 76 (2014).

    Google Scholar 

  86. Slowing, I. I., Wu, C. W., Vivero-Escoto, J. L. & Lin, V. S. Y. Mesoporous silica nanoparticles for reducing hemolytic activity towards mammalian red blood cells. Small 5, 57–62 (2009).

    CAS  Google Scholar 

  87. Lee, J. et al. Simple synthesis of functionalized superparamagnetic magnetite/silica core/shell nanoparticles and their application as magnetically separable high-performance biocatalysts. Small 4, 143–152 (2008).

    CAS  Google Scholar 

  88. Lin, Y.-S. & Haynes, C. L. Impacts of mesoporous silica nanoparticle size, pore ordering, and pore integrity on hemolytic activity. J. Am. Chem. Soc. 132, 4834–4842 (2010).

    CAS  Google Scholar 

  89. Zhao, Y. et al. Interaction of mesoporous silica nanoparticles with human red blood cell membranes: size and surface effects. ACS Nano 5, 1366–1375 (2011).

    CAS  Google Scholar 

  90. Francia, V. et al. Corona composition can affect the mechanisms cells use to internalize nanoparticles. ACS Nano 13, 11107–11121 (2019).

    CAS  Google Scholar 

  91. Lesniak, A. et al. Effects of the presence or absence of a protein corona on silica nanoparticle uptake and impact on cells. ACS Nano 6, 5845–5857 (2012).

    CAS  Google Scholar 

  92. Nel, A. E. et al. Understanding biophysicochemical interactions at the nano–bio interface. Nat. Mater. 8, 543–557 (2009).

    CAS  Google Scholar 

  93. Beddoes, C. M., Case, C. P. & Briscoe, W. H. Understanding nanoparticle cellular entry: a physicochemical perspective. Adv. Colloid Interface Sci. 218, 48–68 (2015).

    CAS  Google Scholar 

  94. Chou, C.-C., Chen, W., Hung, Y. & Mou, C.-Y. Molecular elucidation of biological response to mesoporous silica nanoparticles in vitro and in vivo. ACS Appl. Mater. Interfaces 9, 22235–22251 (2017).

    CAS  Google Scholar 

  95. Meng, H. et al. Aspect ratio determines the quantity of mesoporous silica nanoparticle uptake by a small GTPase-dependent macropinocytosis mechanism. ACS Nano 5, 4434–4447 (2011).

    CAS  Google Scholar 

  96. Porras, M. A. G. et al. Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons. Nanomedicine 14, 661–672 (2018).

    Google Scholar 

  97. Li, Y. et al. The internalization, distribution, and ultrastructure damage of silica nanoparticles in human hepatic L-02 cells. Part. Part. Syst. Charact. 33, 664–674 (2016).

    CAS  Google Scholar 

  98. Oh, N. & Park, J. H. Endocytosis and exocytosis of nanoparticles in mammalian cells. Int. J. Nanomed. 9, 51–63 (2014).

    Google Scholar 

  99. Dostert, C. et al. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320, 674–677 (2008).

    CAS  Google Scholar 

  100. Yang, B., Chen, Y. & Shi, J. Reactive oxygen species (ROS)-based nanomedicine. Chem. Rev. 119, 4881–4985 (2019).

    CAS  Google Scholar 

  101. Guo, C. et al. Silica nanoparticles induced endothelial apoptosis via endoplasmic reticulum stress-mitochondrial apoptotic signaling pathway. Chemosphere 210, 183–192 (2018).

    CAS  Google Scholar 

  102. Chen, Y. et al. Colloidal HPMO nanoparticles: silica-etching chemistry tailoring, topological transformation, and nano-biomedical applications. Adv. Mater. 25, 3100–3105 (2013).

    CAS  Google Scholar 

  103. Sun, B. et al. Reduction of acute inflammatory effects of fumed silica nanoparticles in the lung by adjusting silanol display through calcination and metal doping. ACS Nano 9, 9357–9372 (2015).

    CAS  Google Scholar 

  104. Williams, M. et al. Toxicological Profile for Silica (Agency for Toxic Substances and Disease Registry, 2019).

  105. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Arsenic, Metals, Fibres, and Dusts Vol. 100C 355-397 (International Agency for Research on Cancer, 2012).

  106. Napierska, D., Thomassen, L. C. J., Lison, D., Martens, J. A. & Hoet, P. H. The nanosilica hazard: another variable entity. Part. Fibre Toxicol. 7, 39 (2010).

    CAS  Google Scholar 

  107. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Silica, Some Silicates, Coal Dust and Para-Aramid Fibrils Vol. 68 1–475 (International Agency for Research on Cancer, 1997).

  108. Bryrne, J. D. & Baugh, J. A. The significance of nanoparticles in particle-induced pulmonary fibrosis. McGill J. Med. 11, 43–50 (2008).

    Google Scholar 

  109. Lu, J., Liong, M., Li, Z., Zink, J. I. & Tamanoi, F. Biocompatibility, biodistribution and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals. Small 6, 1794–1805 (2010).

    CAS  Google Scholar 

  110. Fu, C. et al. The absorption, distribution, excretion and toxicity of mesoporous silica nanoparticles in mice following different exposure routes. Biomaterials 34, 2565–2575 (2013).

    CAS  Google Scholar 

  111. Hudson, S. P., Padera, R. F., Langer, R. & Kohane, D. S. The biocompatibility of mesoporous silicates. Biomaterials 29, 4045–4055 (2008).

    CAS  Google Scholar 

  112. He, L., Lai, H. & Chen, T. Dual-function nanosystem for synergetic cancer chemo-/radiotherapy through ROS-mediated signaling pathways. Biomaterials 51, 30–42 (2015).

    CAS  Google Scholar 

  113. Lu, X. et al. Integrated metabonomics analysis of the size-response relationship of silica nanoparticles-induced toxicity in mice. Nanotechnology 22, 055101 (2011).

    Google Scholar 

  114. Nishimori, H. et al. Histological analysis of 70-nm silica particles-induced chronic toxicity in mice. Eur. J. Pharm. Biopharm. 72, 626–629 (2009).

    CAS  Google Scholar 

  115. Xie, G., Sun, J., Zhong, G., Shi, L. & Zhang, D. Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch. Toxicol. 84, 183–190 (2010).

    CAS  Google Scholar 

  116. Bradbury, M. S. et al. Clinically-translated silica nanoparticles as dual-modality cancer-targeted probes for image-guided surgery and interventions. Integr. Biol. 5, 74–86 (2013).

    CAS  Google Scholar 

  117. Kharlamov, A. N. et al. Silica–gold nanoparticles for atheroprotective management of plaques: results of the NANOM-FIM trial. Nanoscale 7, 8003–8015 (2015).

    CAS  Google Scholar 

  118. Phillips, E. et al. Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci. Transl. Med. 6, 260ra149 (2014).

    Google Scholar 

  119. He, Q., Zhang, Z., Gao, F., Li, Y. & Shi, J. In vivo biodistribution and urinary excretion of mesoporous silica nanoparticles: effects of particle size and PEGylation. Small 7, 271–280 (2011).

    CAS  Google Scholar 

  120. Kim, Y.-R. et al. Organization of research team for nano-associated safety assessment in effort to study nanotoxicology of zinc oxide and silica nanoparticles. Int. J. Nanomed. 9, 3–10 (2014).

    CAS  Google Scholar 

  121. Liu, T. et al. Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice. Biomaterials 32, 1657–1668 (2011).

    CAS  Google Scholar 

  122. Guichard, Y. et al. Genotoxicity of synthetic amorphous silica nanoparticles in rats following short-term exposure, part 2: intratracheal instillation and intravenous injection. Environ. Mol. Mutagen. 56, 228–244 (2015).

    CAS  Google Scholar 

  123. Park, E.-J. & Park, K. Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol. Lett. 184, 18–25 (2009).

    CAS  Google Scholar 

  124. Lee, S. et al. The comparative immunotoxicity of mesoporous silica nanoparticles and colloidal silica nanoparticles in mice. Int. J. Nanomed. 8, 147–158 (2013).

    Google Scholar 

  125. Kwon, D. et al. Extra-large pore mesoporous silica nanoparticles for directing in vivo M2 macrophage polarization by delivering IL-4. Nano Lett. 17, 2747–2756 (2017).

    CAS  Google Scholar 

  126. Yamashita, K. et al. Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat. Nanotechnol. 6, 321–328 (2011).

    CAS  Google Scholar 

  127. Cooke, J., DeGabriel, J. L. & Hartley, S. E. The functional ecology of plant silicon: geoscience to genes. Funct. Ecol. 30, 1270–1276 (2016).

    Google Scholar 

  128. Suresh, B. & Yokose, K. Chemical Economics Handbook (CEH) Marketing Research Report: Silicas and Silicates (SRI Consulting, 2011).

  129. Kasaai, M. R. Nanosized particles of silica and its derivatives for applications in various branches of food and nutrition sectors. J. Nanotechnol. 2015, 852394 (2015).

    Google Scholar 

  130. Peters, R. et al. Presence of nano-sized silica during in vitro digestion of foods containing silica as a food additive. ACS Nano 6, 2441–2451 (2012).

    CAS  Google Scholar 

  131. Dekkers, S. et al. Presence and risks of nanosilica in food products. Nanotoxicology 5, 393–405 (2011).

    CAS  Google Scholar 

  132. Reed, R., Schoepf, J., Masles, M. & Westerhoff, P. Detecting Engineered Nanomaterials in Processed Foods From Australia (Arizona State University, 2015).

  133. Athinarayanan, J., Periasamy, V. S., Alsaif, M. A., Al-Warthan, A. A. & Alshatwi, A. A. Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells. Cell Biol. Toxicol. 30, 89–100 (2014).

    CAS  Google Scholar 

  134. Parveen, N. & Ashraf, M. Role of silicon in mitigating the adverse effects of salt stress on growth and photosynthetic attributes of two maize (Zea mays L.) cultivars grown hydroponically. Pak. J. Bot. 42, 1675–1684 (2010).

    CAS  Google Scholar 

  135. Carey, J. C. & Fulweiler, R. W. Human appropriation of biogenic silicon–the increasing role of agriculture. Funct. Ecol. 30, 1331–1339 (2016).

    Google Scholar 

  136. Vance, M. E. et al. Nanotechnology in the real world: redeveloping the nanomaterial consumer products inventory. Beil. J. Nanotechnol. 6, 1769–1780 (2015).

    CAS  Google Scholar 

  137. Liljenström, C., Lazarevic, D. & Finnveden, G. Silicon-Based Nanomaterials in a Life-Cycle Perspective, Including a Case Study on Self-Cleaning Coatings (KTH Royal Institute of Technology, 2013).

  138. Maguire, T. J. & Fulweiler, R. W. Fate and effect of dissolved silicon within wastewater treatment effluent. Environ. Sci. Technol. 51, 7403–7411 (2017).

    CAS  Google Scholar 

  139. Vallet-Regi, M., Ramila, A., Del Real, R. & Pérez-Pariente, J. A new property of MCM-41: drug delivery system. Chem. Mater. 13, 308–311 (2001).

    CAS  Google Scholar 

  140. Baeza, A., Manzano, M., Colilla, M. & Vallet-Regi, M. Recent advances in mesoporous silica nanoparticles for antitumor therapy: our contribution. Biomater. Sci. 4, 803–813 (2016).

    CAS  Google Scholar 

  141. Manzano, M. & Vallet-Regí, M. Mesoporous silica nanoparticles in nanomedicine applications. J. Mater. Sci. 29, 65 (2018).

    Google Scholar 

  142. Chen, F. et al. Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer. Nat. Commun. 9, 4141 (2018).

    Google Scholar 

  143. Wilhelm, S. et al. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 1, 16014 (2016).

    CAS  Google Scholar 

  144. Tamarov, K., Näkki, S., Xu, W. & Lehto, V.-P. Approaches to improve the biocompatibility and systemic circulation of inorganic porous nanoparticles. J. Mater. Chem. B 6, 3632–3649 (2018).

    CAS  Google Scholar 

  145. Dogra, P. et al. Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics. Nat. Commun. 9, 4551 (2018).

    Google Scholar 

  146. Liu, X. et al. In vitro and in vivo evaluation of puerarin-loaded PEGylated mesoporous silica nanoparticles. Drug Dev. Ind. Pharm. 42, 2031–2037 (2016).

    CAS  Google Scholar 

  147. Chen, F. et al. Intrinsic radiolabeling of Titanium-45 using mesoporous silica nanoparticles. Acta Pharmacol. Sin. 38, 907–913 (2017).

    CAS  Google Scholar 

  148. Benezra, M. et al. Multimodal silica nanoparticles are effective cancer-targeted probes in a model of human melanoma. J. Clin. Invest. 121, 2768–2780 (2011).

    CAS  Google Scholar 

  149. Lu, N. et al. Biodegradable hollow mesoporous organosilica nanotheranostics for mild hyperthermia-induced bubble-enhanced oxygen-sensitized radiotherapy. ACS Nano 12, 1580–1591 (2018).

    CAS  Google Scholar 

  150. Huang, P. et al. Molecularly organic/inorganic hybrid hollow mesoporous organosilica nanocapsules with tumor-specific biodegradability and enhanced chemotherapeutic functionality. Biomaterials 125, 23–37 (2017).

    CAS  Google Scholar 

  151. Fan, W. et al. Generic synthesis of small-sized hollow mesoporous organosilica nanoparticles for oxygen-independent X-ray-activated synergistic therapy. Nat. Commun. 10, 1241 (2019).

    Google Scholar 

  152. Lv, R. et al. An imaging-guided platform for synergistic photodynamic/photothermal/chemo-therapy with pH/temperature-responsive drug release. Biomaterials 63, 115–127 (2015).

    CAS  Google Scholar 

  153. Feng, Y. et al. Thermo- and pH-responsive, lipid-coated, mesoporous silica nanoparticle-based dual drug delivery system to improve the antitumor effect of hydrophobic drugs. Mol. Pharm. 16, 422–436 (2019).

    CAS  Google Scholar 

  154. Chen, Y. et al. In vivo distribution and antitumor activity of doxorubicin-loaded N-isopropylacrylamide-co-methacrylic acid coated mesoporous silica nanoparticles and safety evaluation. Eur. J. Pharm. Biopharm. 85, 406–412 (2013).

    CAS  Google Scholar 

  155. Murugan, C. et al. Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy. Sci. Rep. 6, 34053 (2016).

    CAS  Google Scholar 

  156. Gurka, M. K. et al. Identification of pancreatic tumors in vivo with ligand-targeted, pH responsive mesoporous silica nanoparticles by multispectral optoacoustic tomography. J. Control. Release 231, 60–67 (2016).

    CAS  Google Scholar 

  157. Meng, H. et al. Two-wave nanotherapy to target the stroma and optimize gemcitabine delivery to a human pancreatic cancer model in mice. ACS Nano 7, 10048–10065 (2013).

    CAS  Google Scholar 

  158. Hanafi-Bojd, M. Y., Jaafari, M. R., Ramezanian, N., Abnous, K. & Malaekeh-Nikouei, B. Co-delivery of epirubicin and siRNA using functionalized mesoporous silica nanoparticles enhances in vitro and in vivo drug efficacy. Curr. Drug Deliv. 13, 1176–1182 (2016).

    CAS  Google Scholar 

  159. Hanafi-Bojd, M. Y. et al. Surface functionalized mesoporous silica nanoparticles as an effective carrier for epirubicin delivery to cancer cells. Eur. J. Pharm. Biopharm. 89, 248–258 (2015).

    CAS  Google Scholar 

  160. Croissant, J. G. & Guardado-Alvarez, T. M. Photocracking silica: tuning the plasmonic photothermal degradation of mesoporous silica encapsulating gold nanoparticles for cargo release. Inorganics 7, 72 (2019).

    CAS  Google Scholar 

  161. Cheng, W. et al. pH-sensitive delivery vehicle based on folic acid-conjugated polydopamine-modified mesoporous silica nanoparticles for targeted cancer therapy. ACS Appl. Mater. Interfaces 9, 18462–18473 (2017).

    CAS  Google Scholar 

  162. Hu, J. et al. Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats. Oncotarget 7, 73681–73696 (2016).

    Google Scholar 

  163. Wei, Y. et al. Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy. Drug Deliv. 24, 681–691 (2017).

    CAS  Google Scholar 

  164. Biswas, N. Modified mesoporous silica nanoparticles for enhancing oral bioavailability and antihypertensive activity of poorly water soluble valsartan. Eur. J. Pharm. Sci. 99, 152–160 (2017).

    CAS  Google Scholar 

  165. Thiyagarajan, V., Lin, S.-X., Lee, C.-H. & Weng, C.-F. A focal adhesion kinase inhibitor 16-hydroxy-cleroda-3,13-dien-16,15-olide incorporated into enteric-coated nanoparticles for controlled anti-glioma drug delivery. Colloids Surf. B Biointerfaces 141, 120–131 (2016).

    CAS  Google Scholar 

  166. Zou, Z. et al. Programmed packaging of mesoporous silica nanocarriers for matrix metalloprotease 2-triggered tumor targeting and release. Biomaterials 58, 35–45 (2015).

    CAS  Google Scholar 

  167. Zhao, G. et al. Succinylated casein-coated peptide-mesoporous silica nanoparticles as an antibiotic against intestinal bacterial infection. Biomater. Sci. 7, 2440–2451 (2019).

    CAS  Google Scholar 

  168. Li, H. et al. Nucleus-targeted nano delivery system eradicates cancer stem cells by combined thermotherapy and hypoxia-activated chemotherapy. Biomaterials 200, 1–14 (2019).

    CAS  Google Scholar 

  169. Shi, S. et al. In vivo tumor-targeted dual-modality PET/optical imaging with a yolk/shell-structured silica nanosystem. Nano-Micro Lett. 10, 65 (2018).

    Google Scholar 

  170. Chen, W.-H. et al. Mesoporous silica-based versatile theranostic nanoplatform constructed by layer-by-layer assembly for excellent photodynamic/chemo therapy. Biomaterials 117, 54–65 (2016).

    Google Scholar 

  171. Croissant, J. G. et al. Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging. J. Control. Release 229, 183–191 (2016).

    CAS  Google Scholar 

  172. Srivastava, P. et al. Protease-responsive targeted delivery of doxorubicin from bilirubin-BSA-capped mesoporous silica nanoparticles against colon cancer. ACS Biomater. Sci. Eng. 3, 3376–3385 (2017).

    CAS  Google Scholar 

  173. Lu, J. et al. BSA modified, disulfide-bridged mesoporous silica with low biotoxicity for dual-responsive drug delivery. Microporous Mesoporous Mater. 278, 257–266 (2019).

    CAS  Google Scholar 

  174. Chen, W., Glackin, C. A., Horwitz, M. A. & Zink, J. I. Nanomachines and other caps on mesoporous silica nanoparticles for drug delivery. Acc. Chem. Res. 52, 1531–1542 (2019).

    CAS  Google Scholar 

  175. Shahin, S. A. et al. Hyaluronic acid conjugated nanoparticle delivery of siRNA against TWIST reduces tumor burden and enhances sensitivity to cisplatin in ovarian cancer. Nanomedicine 14, 1381–1394 (2018).

    CAS  Google Scholar 

  176. Durfee, P. N. et al. Mesoporous silica nanoparticle-supported lipid bilayers (protocells) for active targeting and delivery to individual leukemia cells. ACS Nano 10, 8325–8345 (2016).

    CAS  Google Scholar 

  177. Lee, Y. K., Lee, H. & Nam, J.-M. Lipid-nanostructure hybrids and their applications in nanobiotechnology. NPG Asia Mater. 5, e48 (2013).

    CAS  Google Scholar 

  178. Alamoudi, K. et al. Thermoresponsive pegylated bubble liposome nanovectors for efficient siRNA delivery via endosomal escape. Nanomedicine 12, 1421–1433 (2017).

    CAS  Google Scholar 

  179. Rideau, E., Dimova, R., Schwille, P., Wurm, F. R. & Landfester, K. Liposomes and polymersomes: a comparative review towards cell mimicking. Chem. Soc. Rev. 47, 8572–8610 (2018).

    CAS  Google Scholar 

  180. Deshpande, S. et al. Spatiotemporal control of coacervate formation within liposomes. Nat. Commun. 10, 1800 (2019).

    Google Scholar 

  181. Correa, S., Boehnke, N., Deiss-Yehiely, E. & Hammond, P. T. Solution conditions tune and optimize loading of therapeutic polyelectrolytes into layer-by-layer functionalized liposomes. ACS Nano 13, 5623–5634 (2019).

    CAS  Google Scholar 

  182. Datz, S., Engelke, H., Schirnding, C. V., Nguye, L. & Bein, T. Lipid bilayer-coated curcumin-based mesoporous organosilica nanoparticles for cellular delivery. Microporous Mesoporous Mater. 225, 371–377 (2016).

    CAS  Google Scholar 

  183. Liu, X. et al. Improved efficacy and reduced toxicity using a custom-designed irinotecan-delivering silicasome for orthotopic colon cancer. ACS Nano 13, 38–53 (2019).

    CAS  Google Scholar 

  184. Liu, X. et al. Tumor-penetrating peptide enhances transcytosis of silicasome-based chemotherapy for pancreatic cancer. J. Clin. Invest. 127, 2007–2018 (2017).

    Google Scholar 

  185. He, Y., Su, Z., Xue, L., Xu, H. & Zhang, C. Co-delivery of erlotinib and doxorubicin by pH-sensitive charge conversion nanocarrier for synergistic therapy. J. Control. Release 229, 80–92 (2016).

    CAS  Google Scholar 

  186. Wang, D. et al. The eradication of breast cancer cells and stem cells by 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticle-supported lipid bilayers containing docetaxel. Biomaterials 34, 7662–7673 (2013).

    CAS  Google Scholar 

  187. Yang, S. et al. Bacteria-targeting nanoparticles with microenvironment-responsive antibiotic release to eliminate intracellular Staphylococcus aureus and associated infection. ACS Appl. Mater. Interfaces 10, 14299–14311 (2018).

    CAS  Google Scholar 

  188. Lu, J. et al. Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression. Nat. Commun. 8, 1811 (2017).

    Google Scholar 

  189. Zhang, X. et al. Biofunctionalized polymer-lipid supported mesoporous silica nanoparticles for release of chemotherapeutics in multidrug resistant cancer cells. Biomaterials 35, 3650–3665 (2014).

    CAS  Google Scholar 

  190. Liu, X. et al. Irinotecan delivery by lipid-coated mesoporous silica nanoparticles shows improved efficacy and safety over liposomes for pancreatic cancer. ACS Nano 10, 2702–2715 (2016).

    CAS  Google Scholar 

  191. Su, J. et al. Enhanced blood suspensibility and laser-activated tumor-specific drug release of theranostic mesoporous silica nanoparticles by functionalizing with erythrocyte membranes. Theranostics 7, 523–537 (2017).

    CAS  Google Scholar 

  192. Xuan, M. et al. Magnetic mesoporous silica nanoparticles cloaked by red blood cell membranes: applications in cancer therapy. Angew. Chem. Int. Ed. 57, 6049–6053 (2018).

    CAS  Google Scholar 

  193. Xuan, M., Shao, J., Dai, L., He, Q. & Li, J. Macrophage cell membrane camouflaged mesoporous silica nanocapsules for in vivo cancer therapy. Adv. Healthc. Mater. 4, 1645–1652 (2015).

    CAS  Google Scholar 

  194. Yu, Z., Zhou, P., Pan, W., Li, N. & Tang, B. A biomimetic nanoreactor for synergistic chemiexcited photodynamic therapy and starvation therapy against tumor metastasis. Nat. Commun. 9, 5044 (2018).

    Google Scholar 

  195. Liu, C. M. et al. Cancer cell membrane-cloaked mesoporous silica nanoparticles with a pH-sensitive gatekeeper for cancer treatment. Colloids Surf. B Biointerfaces 175, 477–486 (2019).

    CAS  Google Scholar 

  196. Butler, K. S. et al. Protocells: modular mesoporous silica nanoparticle-supported lipid bilayers for drug delivery. Small 12, 2173–2185 (2016).

    CAS  Google Scholar 

  197. Coti, K. K. et al. Mechanised nanoparticles for drug delivery. Nanoscale 1, 16–39 (2009).

    CAS  Google Scholar 

  198. Clemens, D. L. et al. Nanoparticle formulation of moxifloxacin and intramuscular route of delivery improve antibiotic pharmacokinetics and treatment of pneumonic tularemia in a mouse model. ACS Infect. Dis. 5, 281–291 (2019).

    CAS  Google Scholar 

  199. Nguyen, T. D. et al. Construction of a pH-driven supramolecular nanovalve. Org. Lett. 8, 3363–3366 (2006).

    CAS  Google Scholar 

  200. Patel, K. et al. Enzyme-responsive snap-top covered silica nanocontainers. J. Am. Chem. Soc. 130, 2382–2383 (2008).

    CAS  Google Scholar 

  201. Croissant, J. et al. Two-photon-triggered drug delivery in cancer cells using nanoimpellers. Angew. Chem. Int. Ed. 125, 14058–14062 (2013).

    Google Scholar 

  202. Croissant, J. G. et al. Disulfide-gated mesoporous silica nanoparticles designed for two-photon-triggered drug release and imaging. J. Mater. Chem. B 3, 6456–6461 (2015).

    CAS  Google Scholar 

  203. Yang, B., Chen, Y. & Shi, J. Exogenous/endogenous-triggered mesoporous silica cancer nanomedicine. Adv. Healthc. Mater. 7, 1800268 (2018).

    Google Scholar 

  204. Nafisi, S., Schafer-Korting, M. & Maibach, H. I. Perspectives on percutaneous penetration: silica nanoparticles. Nanotoxicology 9, 643–657 (2015).

    CAS  Google Scholar 

  205. Wu, J. et al. Functionalized MoS2 nanosheet-capped periodic mesoporous organosilicas as a multifunctional platform for synergistic targeted chemo-photothermal therapy. Chem. Eng. J. 342, 90–102 (2018).

    CAS  Google Scholar 

  206. Tian, W. et al. Periodic mesoporous organosilica coated Prussian blue for MR/PA dual-modal imaging-guided photothermal- chemotherapy of triple negative breast cancer. Adv. Sci. 4, 1600356 (2017).

    Google Scholar 

  207. Campbell, J. L. et al. Multimodal assessment of SERS nanoparticle biodistribution post ingestion reveals new potential for clinical translation of Raman imaging. Biomaterials 135, 42–52 (2017).

    CAS  Google Scholar 

  208. Ryu, H. J. et al. Evaluation of silica nanoparticle toxicity after topical exposure for 90 days. Int. J. Nanomed. 9, 127–136 (2014).

    Google Scholar 

  209. Rancan, F. et al. Skin penetration and cellular uptake of amorphous silica nanoparticles with variable size, surface functionalization, and colloidal stability. ACS Nano 6, 6829–6842 (2012).

    CAS  Google Scholar 

  210. Ostrowski, A. et al. Skin barrier disruptions in tape stripped and allergic dermatitis models have no effect on dermal penetration and systemic distribution of AHAPS-functionalized silica nanoparticles. Nanomedicine 10, 1571–1581 (2014).

    CAS  Google Scholar 

  211. Sutunkova, M. P. et al. A paradoxical response of the rat organism to long-term inhalation of silica-containing submicron (predominantly nanoscale) particles of a collected industrial aerosol at realistic exposure levels. Toxicology 384, 59–68 (2017).

    CAS  Google Scholar 

  212. Garbuzenko, O. B., Mainelis, G., Taratula, O. & Minko, T. Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention. Cancer Biol. Med. 11, 44–55 (2014).

    CAS  Google Scholar 

  213. Kumar, R. et al. In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles. ACS Nano 4, 699–708 (2010).

    CAS  Google Scholar 

  214. Meng, H. et al. Use of size and a copolymer design feature to improve the biodistribution and the enhanced permeability and retention effect of doxorubicin-loaded mesoporous silica nanoparticles in a murine xenograft tumor model. ACS Nano 5, 4131–4144 (2011).

    CAS  Google Scholar 

  215. Taratula, O., Garbuzenko, O. B., Chen, A. M. & Minko, T. Innovative strategy for treatment of lung cancer: targeted nanotechnology-based inhalation co-delivery of anticancer drugs and siRNA. J. Drug Target. 19, 900–914 (2011).

    CAS  Google Scholar 

  216. Goel, S. et al. Engineering intrinsically zirconium-89 radiolabeled self-destructing mesoporous silica nanostructures for in vivo biodistribution and tumor targeting studies. Adv. Sci. 3, 1600122 (2016).

    Google Scholar 

  217. Huang, X. et al. The shape effect of mesoporous silica nanoparticles on biodistribution, clearance, and biocompatibility in vivo. ACS Nano 5, 5390–5399 (2011).

    CAS  Google Scholar 

  218. Malfatti, M. A., Palko, H. A., Kuhn, E. A. & Turteltaub, K. W. Determining the pharmacokinetics and long-term biodistribution of SiO2 nanoparticles in vivo using accelerator mass spectrometry. Nano Lett. 12, 5532–5538 (2012).

    CAS  Google Scholar 

  219. Xie, G., Sun, J. & Zhong, G. Tissular localization and excretion of intravenously administered silica nanoparticles of different sizes. J. Nanoparticle Res. 14, 671–680 (2012).

    Google Scholar 

  220. Souris, J. S. et al. Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles. Biomaterials 31, 5564–5574 (2010).

    CAS  Google Scholar 

  221. Jiao, Y., Sun, Y., Tang, X., Ren, Q. & Yang, W. Tumor-targeting multifunctional rattle-type theranostic nanoparticles for MRI/NIRF bimodal imaging and delivery of hydrophobic drugs. Small 11, 1962–1974 (2015).

    CAS  Google Scholar 

  222. Fang, S. et al. Dual-stimuli responsive nanotheranostics for multimodal imaging guided trimodal synergistic therapy. Small 13, 1602580 (2017).

    Google Scholar 

  223. Xu, C. et al. Bacteria-like mesoporous silica-coated gold nanorods for positron emission tomography and photoacoustic imaging-guided chemo-photothermal combined therapy. Biomaterials 165, 56–65 (2018).

    CAS  Google Scholar 

  224. Hu, H. et al. Mesoporous silica nanoparticles functionalized with fluorescent and MRI reporters for the visualization of murine tumors overexpressing αvβ3 receptors. Nanoscale 8, 7094–7104 (2016).

    CAS  Google Scholar 

  225. Sweeney, S. K., Luo, Y., O’Donnell, M. A. & Assouline, J. Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles. Cancer Nanotechnol. 7, 3 (2016).

    Google Scholar 

  226. Song, J.-T. et al. Facile synthesis of gold nanospheres modified by positively charged mesoporous silica, loaded with near-infrared fluorescent dye, for in vivo X-ray computed tomography and fluorescence dual mode imaging. ACS Appl. Mater. Interfaces 7, 17287–17297 (2015).

    CAS  Google Scholar 

  227. Dréau, D. et al. Mucin-1-antibody-conjugated mesoporous silica nanoparticles for selective breast cancer detection in a mucin-1 transgenic murine mouse model. J. Biomed. Nanotechnol. 12, 2172–2184 (2016).

    Google Scholar 

  228. Shi, J. et al. Multifunctional near infrared-emitting long-persistence luminescent nanoprobes for drug delivery and targeted tumor imaging. Biomaterials 37, 260–270 (2015).

    CAS  Google Scholar 

  229. Croissant, J. G., Zink, J. I., Raehm, L. & Durand, J. O. Two-photon-excited silica and organosilica nanoparticles for spatiotemporal cancer treatment. Adv. Healthc. Mater. 7, 1701248 (2018).

    Google Scholar 

  230. Chen, N.-T. et al. Lectin-functionalized mesoporous silica nanoparticles for endoscopic detection of premalignant colonic lesions. Nanomedicine 13, 1941–1952 (2017).

    CAS  Google Scholar 

  231. Liu, Z. et al. Dual-modality noninvasive mapping of sentinel lymph node by photoacoustic and near-infrared fluorescent imaging using dye-loaded mesoporous silica nanoparticles. Mol. Pharm. 12, 3119–3128 (2015).

    CAS  Google Scholar 

  232. Chen, Y. et al. Stimuli-responsive nanocomposites for magnetic targeting synergistic multimodal therapy and T1/T2-weighted dual-mode imaging. Nanomedicine 13, 875–883 (2017).

    CAS  Google Scholar 

  233. Hurley, K. R. et al. Predictable heating and positive MRI contrast from a mesoporous silica-coated iron oxide nanoparticle. Mol. Pharm. 13, 2172–2183 (2016).

    CAS  Google Scholar 

  234. Zhan, J. et al. Magnetic and pH dual-responsive mesoporous silica nanocomposites for effective and low-toxic photodynamic therapy. Int. J. Nanomed. 12, 2733–2748 (2017).

    CAS  Google Scholar 

  235. Abd-Elrahman, A. A., El Nabarawi, M. A., Hassan, D. H. & Taha, A. A. Ketoprofen mesoporous silica nanoparticles SBA-15 hard geletin capsules: preparation and in vitro/in vivo characterization. Drug Deliv. 23, 3387–3398 (2016).

    CAS  Google Scholar 

  236. Ren, S. et al. Ternary-responsive drug delivery with activatable dual mode contrast-enhanced in vivo imaging. ACS Appl. Mater. Interfaces 10, 31947–31958 (2018).

    CAS  Google Scholar 

  237. Sánchez, A. et al. Hybrid decorated core@shell Janus nanoparticles as a flexible platform for targeted multimodal molecular bioimaging of cancer. ACS Appl. Mater. Interfaces 10, 31032–31043 (2018).

    Google Scholar 

  238. Yin, P. T. et al. Overcoming chemoresistance in cancer via combined microRNA therapeutics with anticancer drugs using multifunctional magnetic core–shell nanoparticles. ACS Appl. Mater. Interfaces 10, 26954–26963 (2018).

    CAS  Google Scholar 

  239. Chi, X. et al. Targeted arsenite-loaded magnetic multifunctional nanoparticles for treatment of hepatocellular carcinoma. Nanotechnology 30, 175101 (2019).

    CAS  Google Scholar 

  240. Chen, C. et al. Nanoscintillator-mediated X-ray inducible photodynamic therapy for in vivo cancer treatment. Nano Lett. 15, 2249–2256 (2015).

    CAS  Google Scholar 

  241. Xu, J. et al. Highly emissive dye-sensitized upconversion nanostructure for dual-photosensitizer photodynamic therapy and bioimaging. ACS Nano 11, 4133–4144 (2017).

    CAS  Google Scholar 

  242. Goel, S. et al. VEGF121-conjugated mesoporous silica nanoparticle: a tumor targeted drug delivery system. ACS Appl. Mater. Interfaces 6, 21677–21685 (2014).

    CAS  Google Scholar 

  243. Kamkaew, A. et al. Cerenkov radiation induced photodynamic therapy using chlorin e6-loaded hollow mesoporous silica nanoparticles. ACS Appl. Mater. Interfaces 8, 26630–26637 (2016).

    CAS  Google Scholar 

  244. Miller, L. et al. Synthesis, characterization, and biodistribution of multiple 89Zr-labeled pore-expanded mesoporous silica nanoparticles for PET. Nanoscale 6, 4928–4935 (2014).

    CAS  Google Scholar 

  245. Chakravarty, R. et al. Functionalized hollow mesoporous silica nanoparticles for tumor vasculature targeting and PET image-guided drug delivery. Nanomedicine 10, 1233–1246 (2015).

    CAS  Google Scholar 

  246. Ellison, P. A. et al. Intrinsic and stable conjugation of thiolated mesoporous silica nanoparticles with radioarsenic. ACS Appl. Mater. Interfaces 9, 6772–6781 (2017).

    CAS  Google Scholar 

  247. Chen, F. et al. In vivo integrity and biological fate of chelator-free zirconium-89-labeled mesoporous silica nanoparticles. ACS Nano 9, 7950–7959 (2015).

    CAS  Google Scholar 

  248. Su, Y. Y. et al. A multifunctional PB@mSiO2–PEG/DOX nanoplatform for combined photothermal–chemotherapy of tumor. ACS Appl. Mater. Interfaces 8, 17038–17046 (2016).

    CAS  Google Scholar 

  249. Gao, F. et al. Biodegradable, pH-sensitive hollow mesoporous organosilica nanoparticle (HMON) with controlled release of pirfenidone and ultrasound-target-microbubble-destruction (UTMD) for pancreatic cancer treatment. Theranostics 9, 6002–6018 (2019).

    CAS  Google Scholar 

  250. Li, X. et al. Aerosol droplet delivery of mesoporous silica nanoparticles: a strategy for respiratory-based therapeutics. Nanomedicine 11, 1377–1385 (2015).

    CAS  Google Scholar 

  251. Wang, T., Liu, Y. & Wu, C. Effect of paclitaxel-mesoporous silica nanoparticles with a core-shell structure on the human lung cancer cell line A549. Nanoscale Res. Lett. 12, 66 (2017).

    Google Scholar 

  252. Desai, D. et al. Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles. Int. J. Nanomed. 11, 299–313 (2016).

    CAS  Google Scholar 

  253. Bukara, K. et al. In vivo performance of fenofibrate formulated with ordered mesoporous silica versus 2-marketed formulations: a comparative bioavailability study in beagle dogs. J. Pharm. Sci. 105, 2381–2385 (2016).

    CAS  Google Scholar 

  254. Zhang, Y. et al. Development of novel mesoporous nanomatrix-supported lipid bilayers for oral sustained delivery of the water-insoluble drug, lovastatin. Colloids Surf. B Biointerfaces 128, 77–85 (2015).

    CAS  Google Scholar 

  255. Farjadian, F., Ghasemi, S., Heidari, R. & Mohammadi-Samani, S. In vitro and in vivo assessment of EDTA-modified silica nano-spheres with supreme capacity of iron capture as a novel antidote agent. Nanomedicine 13, 745–753 (2017).

    CAS  Google Scholar 

  256. Wu, Y. et al. Layer-by-layer (LBL) self-assembled biohybrid nanomaterials for efficient antibacterial applications. ACS Appl. Mater. Interfaces 7, 17255–17263 (2015).

    CAS  Google Scholar 

  257. Dong, R.-H. et al. In situ deposition of a personalized nanofibrous dressing via a handy electrospinning device for skin wound care. Nanoscale 8, 3482–3488 (2016).

    CAS  Google Scholar 

  258. Kim, J.-H., Kim, T.-H., Kang, M. S. & Kim, H.-W. Angiogenic effects of collagen/mesoporous nanoparticle composite scaffold delivering VEGF165. BioMed. Res. Int. 2016, 9676934 (2016).

    Google Scholar 

  259. Qiu, K. et al. Electrophoretic deposition of dexamethasone-loaded mesoporous silica nanoparticles onto poly(l-lactic acid)/poly(ε-caprolactone) composite scaffold for bone tissue engineering. ACS Appl. Mater. Interfaces 8, 4137–4148 (2016).

    CAS  Google Scholar 

  260. Shokry, H. et al. Mesoporous silica particle-PLA–PANI hybrid scaffolds for cell-directed intracellular drug delivery and tissue vascularization. Nanoscale 7, 14434–14443 (2015).

    CAS  Google Scholar 

  261. He, S. et al. Synergistic effect of mesoporous silica and hydroxyapatite in loaded poly(dl-lactic-co-glycolic acid) microspheres on the regeneration of bone defects. BioMed. Res. Int. 2016, 9824827 (2016).

    Google Scholar 

  262. Yuan, Z. et al. Doxorubicin-loaded mesoporous silica nanoparticle composite nanofibers for long-term adjustments of tumor apoptosis. Nanotechnology 27, 245101 (2016).

    Google Scholar 

  263. Wang, W. et al. Controlled release hydrogen sulfide delivery system based on mesoporous silica nanoparticles protects graft endothelium from ischemia–reperfusion injury. Int. J. Nanomed. 11, 3255–3263 (2016).

    CAS  Google Scholar 

  264. Morry, J. et al. Dermal delivery of HSP47 siRNA with NOX4-modulating mesoporous silica-based nanoparticles for treating fibrosis. Biomaterials 66, 41–52 (2015).

    CAS  Google Scholar 

  265. Xie, J. et al. Mesoporous silica particles as a multifunctional delivery system for pain relief in experimental neuropathy. Adv. Healthc. Mater. 5, 1213–1221 (2016).

    CAS  Google Scholar 

  266. Hou, L. et al. Self-regulated carboxyphenylboronic acid-modified mesoporous silica nanoparticles with “touch switch” releasing property for insulin delivery. ACS Appl. Mater. Interfaces 10, 21927–21938 (2018).

    CAS  Google Scholar 

  267. Kuthati, Y., Kankala, R. K., Lin, S.-X., Weng, C.-F. & Lee, C.-H. pH-triggered controllable release of silver–indole-3 acetic acid complexes from mesoporous silica nanoparticles (IBN-4) for effectively killing malignant bacteria. Mol. Pharm. 12, 2289–2304 (2015).

    CAS  Google Scholar 

  268. Wang, Y. et al. Antibiotic-loaded, silver core-embedded mesoporous silica nanovehicles as a synergistic antibacterial agent for the treatment of drug-resistant infections. Biomaterials 101, 207–216 (2016).

    CAS  Google Scholar 

  269. Kim, J. et al. Synergistic oxygen generation and reactive oxygen species scavenging by manganese ferrite/ceria co-decorated nanoparticles for rheumatoid arthritis treatment. ACS Nano 13, 3206–3217 (2019).

    CAS  Google Scholar 

  270. Na, H.-K. et al. Efficient functional delivery of siRNA using mesoporous silica nanoparticles with ultralarge pores. Small 8, 1752–1761 (2012).

    CAS  Google Scholar 

  271. Tsai, P.-H. et al. Dual delivery of HNF4α and cisplatin by mesoporous silica nanoparticles inhibits cancer pluripotency and tumorigenicity in hepatoma-derived CD133-expressing stem cells. ACS Appl. Mater. Interfaces 11, 19808–19818 (2019).

    CAS  Google Scholar 

  272. Wu, M. et al. Photoresponsive nanovehicle for two independent wavelength light-triggered sequential release of P-gp shRNA and doxorubicin to optimize and enhance synergistic therapy of multidrug-resistant cancer. ACS Appl. Mater. Interfaces 10, 19416–19427 (2018).

    CAS  Google Scholar 

  273. Gayam, S. R. et al. An NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo. Nanoscale 8, 12307–12317 (2016).

    CAS  Google Scholar 

  274. Liu, C. et al. In vivo lighted fluorescence via Fenton reaction: approach for imaging of hydrogen peroxide in living systems. Anal. Chem. 88, 3998–4003 (2016).

    CAS  Google Scholar 

  275. Wang, X. et al. Stimulation of in vivo antitumor immunity with hollow mesoporous silica nanospheres. Angew. Chem. Int. Ed. 55, 1899–1903 (2016).

    CAS  Google Scholar 

  276. Wang, X. et al. Hollow structure improved anti-cancer immunity of mesoporous silica nanospheres in vivo. Small 12, 3510–3515 (2016).

    CAS  Google Scholar 

  277. Li, L. et al. In vivo delivery of silica nanorattle encapsulated docetaxel for liver cancer therapy with low toxicity and high efficacy. ACS Nano 4, 6874–6882 (2010).

    CAS  Google Scholar 

  278. Liu, C. et al. Targeted intracellular controlled drug delivery and tumor therapy through in situ forming Ag nanogates on mesoporous silica nanocontainers. ACS Appl. Mater. Interfaces 7, 11930–11938 (2015).

    CAS  Google Scholar 

  279. Khatoon, S. et al. Zwitterionic mesoporous nanoparticles with a bioresponsive gatekeeper for cancer therapy. Acta Biomater. 40, 282–292 (2016).

    CAS  Google Scholar 

  280. Xiao, X. et al. pH-triggered sustained release of arsenic trioxide by polyacrylic acid capped mesoporous silica nanoparticles for solid tumor treatment in vitro and in vivo. J. Biomater. Appl. 31, 23–35 (2016).

    CAS  Google Scholar 

  281. Fang, J. et al. Albumin-MnO2 gated hollow mesoporous silica nanosystem for modulating tumor hypoxia and synergetic therapy of cervical carcinoma. Colloids Surf. B Biointerfaces 179, 250–259 (2019).

    CAS  Google Scholar 

  282. Fang, J. et al. Quercetin and doxorubicin co-delivery using mesoporous silica nanoparticles enhance the efficacy of gastric carcinoma chemotherapy. Int. J. Nanomed. 13, 5113–5126 (2018).

    CAS  Google Scholar 

  283. Dou, Y. et al. CX-5461-loaded nucleolus-targeting nanoplatform for cancer therapy through induction of pro-death autophagy. Acta Biomater. 79, 317–330 (2018).

    Google Scholar 

  284. Finlay, J. et al. Mesoporous silica nanoparticle delivery of chemically modified siRNA against TWIST1 leads to reduced tumor burden. Nanomedicine 11, 1657–1666 (2015).

    CAS  Google Scholar 

  285. Morry, J. et al. Targeted treatment of metastatic breast cancer by PLK1 siRNA delivered by an antioxidant nanoparticle platform. Mol. Cancer Ther. 16, 763–772 (2017).

    CAS  Google Scholar 

  286. Ngamcherdtrakul, W. et al. Cationic polymer modified mesoporous silica nanoparticles for targeted SiRNA delivery to HER2+ breast cancer. Adv. Funct. Mater. 25, 2646–2659 (2015).

    CAS  Google Scholar 

  287. Zhang, J., Guo, S., Zhang, W., Niu, D. & Gong, J. Large-pore mesoporous silica nanospheres as vehicles for delivering TRAF3-shRNA plasmids to Kupffer cells. Biochem. Biophys. Res. Commun. 469, 196–202 (2016).

    CAS  Google Scholar 

  288. Zheng, H., Wen, S., Zhang, Y. & Sun, Z. Organosilane and polyethylene glycol functionalized magnetic mesoporous silica nanoparticles as carriers for CpG immunotherapy in vitro and in vivo. PLoS ONE 10, e0140265 (2015).

    Google Scholar 

  289. Chen, L. et al. Multifunctional redox-responsive mesoporous silica nanoparticles for efficient targeting drug delivery and magnetic resonance imaging. ACS Appl. Mater. Interfaces 8, 33829–33841 (2016).

    CAS  Google Scholar 

  290. Zhao, N. et al. RGD-conjugated mesoporous silica-encapsulated gold nanorods enhance the sensitization of triple-negative breast cancer to megavoltage radiation therapy. Int. J. Nanomed. 11, 5595–5610 (2016).

    CAS  Google Scholar 

  291. Zhou, S. et al. Intracellular pH-responsive and rituximab-conjugated mesoporous silica nanoparticles for targeted drug delivery to lymphoma B cells. J. Exp. Clin. Cancer Res. 36, 24 (2017).

    Google Scholar 

  292. Lee, J. et al. Mesoporous nanocarriers with a stimulus-responsive cyclodextrin gatekeeper for targeting tumor hypoxia. Nanoscale 9, 6901–6909 (2017).

    CAS  Google Scholar 

  293. Yang, D. et al. Reversing cancer multidrug resistance in xenograft models via orchestrating multiple actions of functional mesoporous silica nanoparticles. ACS Appl. Mater. Interfaces 8, 22431–22441 (2016).

    CAS  Google Scholar 

  294. Hu, J.-J. et al. A positive feedback strategy for enhanced chemotherapy based on ROS-triggered self-accelerating drug release nanosystem. Biomaterials 128, 136–146 (2017).

    CAS  Google Scholar 

  295. Lim, W. Q., Phua, S. Z., Xu, H. V., Sreejith, S. & Zhao, Y. Recent advances in multifunctional silica-based hybrid nanocarriers for bioimaging and cancer therapy. Nanoscale 8, 12510–12519 (2016).

    CAS  Google Scholar 

  296. Sun, Q. et al. A photoresponsive and rod-shape nanocarrier: single wavelength of light triggered photothermal and photodynamic therapy based on AuNRs-capped & Ce6-doped mesoporous silica nanorods. Biomaterials 122, 188–200 (2017).

    CAS  Google Scholar 

  297. Tan, S. Y. et al. Responsive mesoporous silica nanoparticles for sensing of hydrogen peroxide and simultaneous treatment toward heart failure. Nanoscale 9, 2253–2261 (2017).

    CAS  Google Scholar 

  298. García-Fernández, A. et al. Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles. J. Control. Release 248, 60–70 (2017).

    Google Scholar 

  299. Duan, F. et al. Metalecarbenicillin framework-based nanoantibiotics with enhanced penetration and highly efficient inhibition of MRSA. Biomaterials 144, 155–165 (2017).

    CAS  Google Scholar 

  300. Obata, F., Fons, C. O. & Gould, A. P. Early-life exposure to low-dose oxidants can increase longevity via microbiome remodelling in Drosophila. Nat. Commun. 9, 975 (2018).

    Google Scholar 

  301. Grodzinski, P., Kircher, M., Goldberg, M. & Gabizon, A. Integrating nanotechnology into cancer care. ACS Nano 13, 7370–7376 (2019).

    CAS  Google Scholar 

  302. Fan, W., Yung, B., Huang, P. & Chen, X. Nanotechnology for multimodal synergistic cancer therapy. Chem. Rev. 117, 13566–13638 (2017).

    CAS  Google Scholar 

  303. Liu, X. et al. MAPK-targeted drug delivered by a pH-sensitive MSNP nanocarrier synergizes with PD-1 blockade in melanoma without T-cell suppression. Adv. Funct. Mater. 29, 1806916 (2019).

    Google Scholar 

  304. Wang, X. et al. Comprehensive mechanism analysis of mesoporous-silica-nanoparticle-induced cancer immunotherapy. Adv. Healthc. Mater. 5, 1169–1176 (2016).

    CAS  Google Scholar 

  305. Ma, M. et al. Bi2S3-embedded mesoporous silica nanoparticles for efficient drug delivery and interstitial radiotherapy sensitization. Biomaterials 37, 447–455 (2015).

    CAS  Google Scholar 

  306. Meng, H. et al. Codelivery of an optimal drug/siRNA combination using mesoporous silica nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo. ACS Nano 7, 994–1005 (2013).

    CAS  Google Scholar 

  307. Credi, A., Balzani, V., Langford, S. J. & Stoddart, J. F. Logic operations at the molecular level. An XOR gate based on a molecular machine. J. Am. Chem. Soc. 119, 2679–2681 (1997).

    CAS  Google Scholar 

  308. Faria, M. et al. Minimum information reporting in bio–nano experimental literature. Nat. Nanotechnol. 13, 777–785 (2018).

    CAS  Google Scholar 

  309. Leong, H. S. et al. On the issue of transparency and reproducibility in nanomedicine. Nat. Nanotechnol. 14, 629–635 (2019).

    CAS  Google Scholar 

  310. Maggini, L., Travaglini, L., Cabrera, I., Castro-Hartmann, P. & De Cola, L. Biodegradable peptide–silica nanodonuts. Chem. Eur. J. 22, 3697–3703 (2016).

    CAS  Google Scholar 

  311. Xu, Z., H., L., Tian, H. & Yan, F. Real-time imaging tracking of engineered macrophages as ultrasound-triggered cell bombs for cancer treatment. Adv. Funct. Mater. 30, 1910304 (2020).

    CAS  Google Scholar 

  312. Tarn, D. et al. Mesoporous silica nanoparticle nanocarriers: biofunctionality and biocompatibility. Acc. Chem. Res. 46, 792–801 (2013).

    CAS  Google Scholar 

  313. Schlegel, M. L., Nagy, K. L., Fenter, P. & Sturchio, N. C. Structures of quartz (100)- and (101)-water interfaces determined by x-ray reflectivity and atomic force microscopy of natural growth surfaces. Geochim. Cosmochim. Acta 66, 3037–3054 (2002).

    CAS  Google Scholar 

  314. Le Page, M., Beau, R. & Duchene, J. Porous silica particles containing a crystallized phase and method. US Patent US 3,493,341A (1970).

  315. Chiola, V., Ritsko, J. E. & Vanderpool, C. D. Process for producing low-bulk density silica. US Patent US 3,556,725A (1971).

  316. Chia, S., Cao, J., Stoddart, J. F. & Zink, J. I. Working supramolecular machines trapped in glass and mounted on a film surface. Angew. Chem. Int. Ed. 40, 2447–2451 (2001).

    CAS  Google Scholar 

  317. Hernandez, R., Tseng, H.-R., Wong, J. W., Stoddart, J. F. & Zink, J. I. An operational supramolecular nanovalve. J. Am. Chem. Soc. 126, 3370–3371 (2004).

    CAS  Google Scholar 

  318. Tsai, C.-P., Chen, C.-Y., Hung, Y., Chang, F.-H. & Mou, C.-Y. Monoclonal antibody-functionalized mesoporous silica nanoparticles (MSN) for selective targeting breast cancer cells. J. Mater. Chem. 19, 5737–5743 (2009).

    CAS  Google Scholar 

  319. Wolf, B., Lam, S., Kirkland, M. & Frith, W. J. Shear thickening of an emulsion stabilized with hydrophilic silica particles. J. Rheol. 51, 465–478 (2007).

    CAS  Google Scholar 

  320. Hu, J. et al. Solid polymer electrolyte based on ionic bond or covalent bond functionalized silica nanoparticles. RSC Adv. 7, 54986–54994 (2017).

    CAS  Google Scholar 

  321. Hsueh, H. Y., Yao, C. T. & Ho, R. M. Well-ordered nanohybrids and nanoporous materials from gyroid block copolymer templates. Chem. Soc. Rev. 44, 1974–2018 (2015).

    CAS  Google Scholar 

  322. Liz-Marzán, L., Giersig, M. & Mulvaney, P. Synthesis of nanosized gold–silica core–shell particles. Langmuir 12, 4329–4335 (1996).

    Google Scholar 

  323. Asefa, T., MacLachlan, M. J., Coombs, N. & Ozin, G. A. Periodic mesoporous organosilicas with organic groups inside the channel walls. Nature 402, 867–871 (1999).

    CAS  Google Scholar 

  324. Hah, H. J., Kim, J. S., Jeon, B. J., Koo, S. M. & Lee, Y. E. Simple preparation of monodisperse hollow silica particles without using templates. Chem. Commun. 2003, 1712–1713 (2003).

    Google Scholar 

  325. Mei, X. et al. Hollow mesoporous silica nanoparticles conjugated with pH-sensitive amphiphilic diblock polymer for controlled drug release. Microporous Mesoporous Mater. 152, 16–24 (2012).

    CAS  Google Scholar 

  326. Mornet, S., Lambert, O., Duguet, E. & Brisson, A. The formation of supported lipid bilayers on silica nanoparticles revealed by cryoelectron microscopy. Nano Lett. 5, 281–285 (2004).

    Google Scholar 

  327. Ashley, C. E. et al. The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers. Nat. Mater. 10, 389–397 (2011).

    CAS  Google Scholar 

  328. Shen, D. et al. Biphase stratification approach to three-dimensional dendritic biodegradable mesoporous silica nanospheres. Nano Lett. 14, 923–932 (2014).

    CAS  Google Scholar 

  329. Ma, K. et al. Self-assembly of highly symmetrical, ultrasmall inorganic cages directed by surfactant micelles. Nature 558, 577–580 (2018).

    CAS  Google Scholar 

  330. Cabrera, Y., Cabrera, A., Larsen, F. H. & Felby, C. Solid-state 29Si NMR and FTIR analyses of lignin-silica coprecipitates. Holzforschung 70, 709–718 (2016).

    CAS  Google Scholar 

  331. De Haan, J. W., Van Den Bogaert, H. M., Ponjeé, J. J. & Van De Ven, L. J. M. Characterization of modified silica powders by Fourier transform infrared spectroscopy and cross-polarization magic angle spinning NMR. J. Colloid Interface Sci. 110, 591–600 (1986).

    Google Scholar 

  332. Liu, C. C. & Maciel, G. E. The fumed silica surface: a study by NMR. J. Am. Chem. Soc. 118, 5103–5119 (1996).

    CAS  Google Scholar 

  333. Kempen, P. J. et al. Theranostic mesoporous silica nanoparticles biodegrade after pro-survival drug delivery and ultrasound/magnetic resonance imaging of stem cells. Theranostics 5, 631–642 (2015).

    CAS  Google Scholar 

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Acknowledgements

This work was supported in part by the U.S. National Institutes of Health under contract number 1 R01 CA226537-01. K.S.B. acknowledges support by the Laboratory Directed Research & Development program at Sandia National Laboratories. Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy National Nuclear Security Administration under contract DE-NA-0003525. Any subjective views or opinions that might be expressed in the paper do not necessarily represent the views of the U.S. Department of Energy or the U.S. Government.

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Authors and Affiliations

  1. Chemical and Biological Engineering, University of New Mexico, Albuquerque, NM, USA

    Jonas G. Croissant & C. Jeffrey Brinker

  2. Center for Micro-Engineered Materials, Advanced Materials Laboratory, University of New Mexico, Albuquerque, NM, USA

    Jonas G. Croissant & C. Jeffrey Brinker

  3. Department of Nanobiology, Sandia National Laboratories, Albuquerque, NM, USA

    Kimberly S. Butler

  4. Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA

    Jeffrey I. Zink

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C.J.B. contributed to the writing and revision of the manuscript. J.G.C. contributed to the literature research, writing of the manuscript and the design of the display items. K.S.B. contributed to the literature research, writing and revision of the manuscript. J.I.Z. contributed to the writing and revision of the manuscript.

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Croissant, J.G., Butler, K.S., Zink, J.I. et al. Synthetic amorphous silica nanoparticles: toxicity, biomedical and environmental implications. Nat Rev Mater 5, 886–909 (2020). https://doi.org/10.1038/s41578-020-0230-0

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