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  • Review Article
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Spatial and temporal control of chemical processes

Abstract

Controlling the where and when of a chemical reaction, rather than just the if, can be an essential component in the successful development of applications. There are a large number of situations in which a predetermined sequence of chemical reaction events might be highly beneficial. In this Review, we examine the development of such spatiotemporal control of chemical reactions. We classify the means of control into either passive or active approaches. The passive approach relies on characteristics inherent to the chosen chemical system in order to predict where and when a reaction will occur. The active strategy, on the other hand, relies on the input of an external stimulus to remotely control the onset of a chemical reaction. Among active methods, we distinguish two different strategies — either remote activation of a reaction or controlled release of chemicals. This versatile toolbox allows spatiotemporal control to be achieved in myriad situations and thus to address some key challenges in chemistry, such as drug delivery.

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Fig. 1: Passive methods allowing temporal and spatial control over chemical reactions.
Fig. 2: Active methods: photoactivation of click reactions.
Fig. 3: Active methods: photocaged chemical compounds involved in click reactions.
Fig. 4: Active methods: photoinduced cycloadditions.
Fig. 5: Active methods: controlled release of chemicals through metallic containers and microdroplets.
Fig. 6: Active methods: controlled release of chemicals through enzyme reactors.
Fig. 7: Active methods: controlled release of chemicals through 3D-printed microparticles and supramolecular assemblies.

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References

  1. Advincula, R. C. Review of conjugated polymer synthesis: methods and reactions conjugated polymer synthesis: methods and reactions. J. Am. Chem. Soc. 133, 5622 (2011).

    Article  CAS  Google Scholar 

  2. Chen, W.-L., Cordero, R., Tran, H. & Ober, C. K. Polymer brushes: novel surfaces for future materials. Macromolecules 50, 4089–4113 (2017).

    Article  CAS  Google Scholar 

  3. Nemani, S. K. et al. Surface modification of polymers: methods and applications. Adv. Mater. Interfaces 5, 1801247 (2018).

    Article  CAS  Google Scholar 

  4. Wang, Y., Feng, L. & Wang, S. Conjugated polymer nanoparticles for imaging, cell activity regulation, and therapy. Adv. Funct. Mater. 29, 1806818 (2019).

    Article  CAS  Google Scholar 

  5. García-Fernández, L. et al. Dual photosensitive polymers with wavelength-selective photoresponse. Adv. Mater. 26, 5012–5017 (2014).

    Article  PubMed  CAS  Google Scholar 

  6. Kaupp, M. et al. Wavelength selective polymer network formation of end-functional star polymers. Chem. Commun. 52, 1975–1978 (2016).

    Article  CAS  Google Scholar 

  7. Zhang, X., Xi, W., Huang, S., Long, K. & Bowman, C. N. Wavelength-selective sequential polymer network formation controlled with a two-color responsive initiation system. Macromolecules 50, 5652–5660 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Blasco, E., Wegener, M. & Barner-Kowollik, C. Photochemically driven polymeric network formation: synthesis and applications. Adv. Mater. 29, 1604005 (2017).

    Article  CAS  Google Scholar 

  9. Tsai, I. Y., Crosby, A. J. & Russell, T. P. in Methods in Cell Biology Vol. 83 Ch. 4 (eds Wang, Y.-L. & Discher, D. E.) 67–87 (Elsevier, 2007).

  10. Leijten, J. et al. Spatially and temporally controlled hydrogels for tissue engineering. Mater. Sci. Eng. R Rep. 119, 1–35 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Heinz, O., Aghajani, M., Greenberg, A. R. & Ding, Y. Surface-patterning of polymeric membranes: fabrication and performance. Curr. Opin. Chem. Eng. 20, 1–12 (2018).

    Article  Google Scholar 

  12. Pickens, C. J., Johnson, S. N., Pressnall, M. M., Leon, M. A. & Berkland, C. J. Practical considerations, challenges, and limitations of bioconjugation via azide–alkyne cycloaddition. Bioconjug. Chem. 29, 686–701 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jiao, M. et al. Recent advancements in biocompatible inorganic nanoparticles towards biomedical applications. Biomater. Sci. 6, 726–745 (2018).

    Article  CAS  PubMed  Google Scholar 

  14. Valcourt, D. M. et al. Advances in targeted nanotherapeutics: from bioconjugation to biomimicry. Nano Res. 11, 4999–5016 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sivaram, A. J., Wardiana, A., Howard, C. B., Mahler, S. M. & Thurecht, K. J. Recent advances in the generation of antibody-nanomaterial conjugates. Adv. Healthc. Mater. 7, 1700607 (2018).

    Article  CAS  Google Scholar 

  16. Sanchis, A., Salvador, J.-P. & Marco, M.-P. Light-induced mechanisms for nanocarrier’s cargo release. Colloids Surf. B Biointerfaces 173, 825–832 (2019).

    Article  CAS  PubMed  Google Scholar 

  17. Reeβing, F. & Szymanski, W. Following nanomedicine activation with magnetic resonance imaging: why, how, and what’s next? Curr. Opin. Biotechnol. 58, 9–18 (2019).

    Article  PubMed  CAS  Google Scholar 

  18. Jiang, Y., Chekuri, S., Fang, R. H. & Zhang, L. Engineering biological interactions on the nanoscale. Curr. Opin. Biotechnol. 58, 1–8 (2019).

    Article  CAS  PubMed  Google Scholar 

  19. Hossen, S. et al. Smart nanocarrier-based drug delivery systems for cancer therapy and toxicity studies: a review. J. Adv. Res. 15, 1–18 (2019).

    Article  PubMed  CAS  Google Scholar 

  20. Norris, M. D., Seidel, K. & Kirschning, A. Externally induced drug release systems with magnetic nanoparticle carriers: an emerging field in nanomedicine. Adv. Ther. 2, 1800092 (2019).

    Article  Google Scholar 

  21. Gulfam, M., Sahle, F. F. & Lowe, T. L. Design strategies for chemical-stimuli-responsive programmable nanotherapeutics. Drug Discov. Today 24, 129–147 (2019).

    Article  CAS  PubMed  Google Scholar 

  22. McIlwaine, R., Kovacs, K., Scott, S. K. & Taylor, A. F. A novel route to pH oscillators. Chem. Phys. Lett. 417, 39–42 (2006).

    Article  CAS  Google Scholar 

  23. Hu, G., Bounds, C., Pojman, J. A. & Taylor, A. F. Time-lapse thiol-acrylate polymerization using a pH clock reaction. J. Polym. Sci. Part Polym. Chem. 48, 2955–2959 (2010).

    Article  CAS  Google Scholar 

  24. Kovacs, K., McIlwaine, R. E., Scott, S. K. & Taylor, A. F. An organic-based pH oscillator. J. Phys. Chem. A 111, 549–551 (2007).

    Article  CAS  PubMed  Google Scholar 

  25. Tóth-Szeles, E. et al. Chemically coded time-programmed self-assembly. Mol. Syst. Des. Eng. 2, 274–282 (2017).

    Article  Google Scholar 

  26. Hu, G., Pojman, J. A., Scott, S. K., Wrobel, M. M. & Taylor, A. F. Base-catalyzed feedback in the urea−urease reaction. J. Phys. Chem. B 114, 14059–14063 (2010).

    Article  CAS  PubMed  Google Scholar 

  27. Muzika, F., Bánsági, T., Schreiber, I., Schreiberová, L. & Taylor, A. F. A bistable switch in pH in urease-loaded alginate beads. Chem. Commun. 50, 11107–11109 (2014).

    Article  CAS  Google Scholar 

  28. Jee, E., Bánsági, T., Taylor, A. F. & Pojman, J. A. Temporal control of gelation and polymerization fronts driven by an autocatalytic enzyme reaction. Angew. Chem. Int. Ed. 55, 2127–2131 (2016).

    Article  CAS  Google Scholar 

  29. Chatani, S., Sheridan, R. J., Podgórski, M., Nair, D. P. & Bowman, C. N. Temporal control of thiol-click chemistry. Chem. Mater. 25, 3897–3901 (2013).

    Article  CAS  Google Scholar 

  30. Arnold, R. M. & Locklin, J. Self-sorting click reactions that generate spatially controlled chemical functionality on surfaces. Langmuir 29, 5920–5926 (2013).

    Article  CAS  PubMed  Google Scholar 

  31. Arnold, R. M., McNitt, C. D., Popik, V. V. & Locklin, J. Direct grafting of poly(pentafluorophenyl acrylate) onto oxides: versatile substrates for reactive microcapillary printing and self-sorting modification. Chem. Commun. 50, 5307–5309 (2014).

    Article  CAS  Google Scholar 

  32. Arnold, R. M., Patton, D. L., Popik, V. V. & Locklin, J. A dynamic duo: pairing click chemistry and postpolymerization modification to design complex surfaces. Acc. Chem. Res. 47, 2999–3008 (2014).

    Article  CAS  PubMed  Google Scholar 

  33. Brooks, K. et al. Multifunctional surface manipulation using orthogonal click chemistry. Langmuir 32, 6600–6605 (2016).

    Article  CAS  Google Scholar 

  34. Yu, H., Li, J., Wu, D., Qiu, Z. & Zhang, Y. Chemistry and biological applications of photo-labile organic molecules. Chem. Soc. Rev. 39, 464–473 (2010).

    Article  PubMed  Google Scholar 

  35. Klán, P. et al. Photoremovable protecting groups in chemistry and biology: reaction mechanisms and efficacy. Chem. Rev. 113, 119–191 (2013).

    Article  PubMed  CAS  Google Scholar 

  36. Göstl, R., Senf, A. & Hecht, S. Remote-controlling chemical reactions by light: towards chemistry with high spatio-temporal resolution. Chem. Soc. Rev. 43, 1982–1996 (2014).

    Article  PubMed  CAS  Google Scholar 

  37. Brimioulle, R., Lenhart, D., Maturi, M. M. & Bach, T. Enantioselective catalysis of photochemical reactions. Angew. Chem. Int. Ed. 54, 3872–3890 (2015).

    Article  CAS  Google Scholar 

  38. Glusac, K. What has light ever done for chemistry? Nat. Chem. 8, 734–735 (2016).

    Article  CAS  PubMed  Google Scholar 

  39. Tasdelen, M. A. & Yagci, Y. Light-induced click reactions. Angew. Chem. Int. Ed. 52, 5930–5938 (2013).

    Article  CAS  Google Scholar 

  40. Ramil, C. P. & Lin, Q. Bioorthogonal chemistry: strategies and recent developments. Chem. Commun. 49, 11007–11022 (2013).

    Article  CAS  Google Scholar 

  41. Herner, A. & Lin, Q. Photo-triggered click chemistry for biological applications. Top. Curr. Chem. 374, 1 (2016).

    Article  CAS  Google Scholar 

  42. Madl, C. M. & Heilshorn, S. C. Bioorthogonal strategies for engineering extracellular matrices. Adv. Funct. Mater. 28, 1706046 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Qin, L.-H., Hu, W. & Long, Y.-Q. Bioorthogonal chemistry: optimization and application updates during 2013–2017. Tetrahedron Lett. 59, 2214–2228 (2018).

    Article  CAS  Google Scholar 

  44. Ji, X. et al. Click and release: bioorthogonal approaches to “on-demand” activation of prodrugs. Chem. Soc. Rev. 48, 1077–1094 (2019).

    Article  CAS  PubMed  Google Scholar 

  45. Bach, T. & Hehn, J. P. Photochemical reactions as key steps in natural product synthesis. Angew. Chem. Int. Ed. 50, 1000–1045 (2011).

    Article  CAS  Google Scholar 

  46. Kaur, G., Johnston, P. & Saito, K. Photo-reversible dimerisation reactions and their applications in polymeric systems. Polym. Chem. 5, 2171–2186 (2014).

    Article  CAS  Google Scholar 

  47. Vidavsky, Y. & Lemcoff, N. G. Light-induced olefin metathesis. Beilstein J. Org. Chem. 6, 1106–1119 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Eivgi, O. & Lemcoff, N. Turning the light on: recent developments in photoinduced olefin metathesis. Synthesis 50, 49–63 (2018).

    Article  CAS  Google Scholar 

  49. Poloukhtine, A. A., Mbua, N. E., Wolfert, M. A., Boons, G.-J. & Popik, V. V. Selective labeling of living cells by a photo-triggered click reaction. J. Am. Chem. Soc. 131, 15769–15776 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Nainar, S. et al. Temporal labeling of nascent rna using photoclick chemistry in live cells. J. Am. Chem. Soc. 139, 8090–8093 (2017).

    Article  CAS  PubMed  Google Scholar 

  51. Orski, S. V. et al. High density orthogonal surface immobilization via photoactivated copper-free click chemistry. J. Am. Chem. Soc. 132, 11024–11026 (2010).

    Article  CAS  PubMed  Google Scholar 

  52. Weissleder, R. A clearer vision for in vivo imaging.pdf. Nat. Biotechnol. 19, 316–317 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Svoboda, K. & Yasuda, R. Principles of two-photon excitation microscopy and its applications to neuroscience. Neuron 50, 823–839 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Urdabayev, N. K., Poloukhtine, A. & Popik, V. V. Two-photon induced photodecarbonylation reaction of cyclopropenones. Chem. Commun. 2006, 454–456 (2006).

    Article  Google Scholar 

  55. McNitt, C. D., Cheng, H., Ullrich, S., Popik, V. V. & Bjerknes, M. Multiphoton activation of photo-strain-promoted azide alkyne cycloaddition “click” reagents enables in situ labeling with submicrometer resolution. J. Am. Chem. Soc. 139, 14029–14032 (2017).

    Article  CAS  PubMed  Google Scholar 

  56. Pauloehrl, T. et al. Adding spatial control to click chemistry: phototriggered Diels–Alder surface (bio)functionalization at ambient temperature. Angew. Chem. Int. Ed. 51, 1071–1074 (2011).

    Article  CAS  Google Scholar 

  57. Krappitz, T. et al. Polymer networks based on photo-caged diene dimerization. Mater. Horiz. 6, 81–89 (2019).

    Article  CAS  Google Scholar 

  58. Claus, T. K. et al. Simultaneous dual encoding of three-dimensional structures by light-induced modular ligation. Angew. Chem. Int. Ed. 55, 3817–3822 (2016).

    Article  CAS  Google Scholar 

  59. Richter, B. et al. Guiding cell attachment in 3D microscaffolds selectively functionalized with two distinct adhesion proteins. Adv. Mater. 29, 1604342 (2017).

    Article  CAS  Google Scholar 

  60. Hiltebrandt, K., Elies, K., D’hooge, D. R., Blinco, J. P. & Barner-Kowollik, C. A light-activated reaction manifold. J. Am. Chem. Soc. 138, 7048–7054 (2016).

    Article  CAS  PubMed  Google Scholar 

  61. Houck, H. A., Du Prez, F. E. & Barner-Kowollik, C. Controlling thermal reactivity with different colors of light. Nat. Commun. 8, 1869 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Feng, W. et al. UV-induced tetrazole–thiol reaction for polymer conjugation and surface functionalization. Angew. Chem. Int. Ed. 54, 8732–8735 (2015).

    Article  CAS  Google Scholar 

  63. Arumugam, S. & Popik, V. V. Patterned surface derivatization using Diels–Alder photoclick reaction. J. Am. Chem. Soc. 133, 15730–15736 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Gungor, E. & Armani, A. M. Photocleavage of covalently immobilized amphiphilic block copolymer: from bilayer to monolayer. Macromolecules 49, 5773–5781 (2016).

    Article  CAS  Google Scholar 

  65. Arumugam, S. & Popik, V. V. Attach, remove, or replace: reversible surface functionalization using thiol–quinone methide photoclick chemistry. J. Am. Chem. Soc. 134, 8408–8411 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Adzima, B. J. et al. Spatial and temporal control of the alkyne–azide cycloaddition by photoinitiated Cu(II) reduction. Nat. Chem. 3, 256–259 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Alzahrani, A. A., Erbse, A. H. & Bowman, C. N. Evaluation and development of novel photoinitiator complexes for photoinitiating the copper-catalyzed azide–alkyne cycloaddition reaction. Polym. Chem. 5, 1874–1882 (2014).

    Article  CAS  Google Scholar 

  68. Hardy, M. D., Konetski, D., Bowman, C. N. & Devaraj, N. K. Ruthenium photoredox-triggered phospholipid membrane formation. Org. Biomol. Chem. 14, 5555–5558 (2016).

    Article  CAS  PubMed  Google Scholar 

  69. Konetski, D., Gong, T. & Bowman, C. N. Photoinduced vesicle formation via the copper-catalyzed azide–alkyne cycloaddition reaction. Langmuir 32, 8195–8201 (2016).

    Article  CAS  PubMed  Google Scholar 

  70. Chen, R. T. et al. Photoinitiated alkyne–azide click and radical cross-linking reactions for the patterning of peg hydrogels. Biomacromolecules 13, 889–895 (2012).

    Article  CAS  PubMed  Google Scholar 

  71. Frazier, C. P., Palmer, L. I., Samoshin, A. V. & Read de Alaniz, J. Accessing nitrosocarbonyl compounds with temporal and spatial control via the photoredox oxidation of N-substituted hydroxylamines. Tetrahedron Lett. 56, 3353–3357 (2015).

    Article  CAS  Google Scholar 

  72. Nguyen, J. D., Tucker, J. W., Konieczynska, M. D. & Stephenson, C. R. J. Intermolecular atom transfer radical addition to olefins mediated by oxidative quenching of photoredox catalysts. J. Am. Chem. Soc. 133, 4160–4163 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Nair, D. P. et al. The thiol–Michael addition click reaction: a powerful and widely used tool in materials chemistry. Chem. Mater. 26, 724–744 (2014).

    Article  CAS  Google Scholar 

  74. DeForest, C. A., Polizzotti, B. D. & Anseth, K. S. Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments. Nat. Mater. 8, 659–664 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Xi, W. et al. Spatial and temporal control of thiol-Michael addition via photocaged superbase in photopatterning and two-stage polymer networks formation. Macromolecules 47, 6159–6165 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Xu, R., Guan, X., He, M. & Yang, J. Phototriggered base proliferation: a powerful 365 nm LED photoclick tool for nucleophile-initiated thiol-Michael addition reaction. RSC Adv. 7, 914–918 (2017).

    Article  CAS  Google Scholar 

  77. Arimitsu, K., Miyamoto, M. & Ichimura, K. Applications of a nonlinear organic reaction of carbamates to proliferate aliphatic amines. Angew. Chem. Int. Ed. 39, 3425–3428 (2000).

    Article  CAS  Google Scholar 

  78. Zhang, X., Xi, W., Wang, C., Podgórski, M. & Bowman, C. N. Visible-light-initiated thiol–Michael addition polymerizations with coumarin-based photobase generators: another photoclick reaction strategy. ACS Macro Lett. 5, 229–233 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Liu, Z. et al. Spatiotemporally controllable and cytocompatible approach builds 3D cell culture matrix by photo-uncaged-thiol Michael addition reaction. Adv. Mater. 26, 3912–3917 (2014).

    Article  CAS  PubMed  Google Scholar 

  80. Yang, Y., Li, Y., Lin, Q., Bao, C. & Zhu, L. In situ phototriggered disulfide-cross-link nanoparticles for drug delivery. ACS Macro Lett. 5, 301–305 (2016).

    Article  CAS  PubMed  Google Scholar 

  81. Liu, Z., Liu, T., Lin, Q., Bao, C. & Zhu, L. Sequential control over thiol click chemistry by a reversibly photoactivated thiol mechanism of spirothiopyran. Angew. Chem. Int. Ed. 54, 174–178 (2014).

    Article  CAS  Google Scholar 

  82. Ramil, C. P. et al. Spirohexene–tetrazine ligation enables bioorthogonal labeling of class B G protein-coupled receptors in live cells. J. Am. Chem. Soc. 139, 13376–13386 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kumar, P., Jiang, T., Li, S., Zainul, O. & Laughlin, S. T. Caged cyclopropenes for controlling bioorthogonal reactivity. Org. Biomol. Chem. 16, 4081–4085 (2018).

    Article  CAS  PubMed  Google Scholar 

  84. Shah, L., Laughlin, S. T. & Carrico, I. S. Light-activated Staudinger–Bertozzi ligation within living animals. J. Am. Chem. Soc. 138, 5186–5189 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Frisch, H., Marschner, D. E., Goldmann, A. S. & Barner-Kowollik, C. Wavelength-gated dynamic covalent chemistry. Angew. Chem. Int. Ed. 57, 2036–2045 (2018).

    Article  CAS  Google Scholar 

  86. Doi, T., Kawai, H., Murayama, K., Kashida, H. & Asanuma, H. Visible-light-triggered cross-linking of DNA duplexes by reversible [2 + 2] photocycloaddition of styrylpyrene. Chem. Eur. J. 22, 10533–10538 (2016).

    Article  CAS  PubMed  Google Scholar 

  87. Marschner, D. E. et al. Visible light [2 + 2] cycloadditions for reversible polymer ligation. Macromolecules 51, 3802–3807 (2018).

    Article  CAS  Google Scholar 

  88. Truong, V. X., Li, F., Ercole, F. & Forsythe, J. S. Wavelength-selective coupling and decoupling of polymer chains via reversible [2 + 2] photocycloaddition of styrylpyrene for construction of cytocompatible photodynamic hydrogels. ACS Macro Lett. 7, 464–469 (2018).

    Article  CAS  PubMed  Google Scholar 

  89. Teator, A. J. & Bielawski, C. W. Remote control Grubbs catalysts that modulate ring-opening metathesis polymerizations. J. Polym. Sci. Part Polym. Chem. 55, 2949–2960 (2017).

    Article  CAS  Google Scholar 

  90. Blanco, V., Leigh, D. A. & Marcos, V. Artificial switchable catalysts. Chem. Soc. Rev. 44, 5341–5370 (2015).

    Article  CAS  PubMed  Google Scholar 

  91. Theunissen, C., Ashley, M. A. & Rovis, T. Visible-light-controlled ruthenium-catalyzed olefin metathesis. J. Am. Chem. Soc. 141, 6791–6796 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Teator, A. J., Shao, H., Lu, G., Liu, P. & Bielawski, C. W. A photoswitchable olefin metathesis catalyst. Organometallics 36, 490–497 (2017).

    Article  CAS  Google Scholar 

  93. Kalinin, Y. V., Murali, A. & Gracias, D. H. Chemistry with spatial control using particles and streams. RSC Adv. 2, 9707–9726 (2012).

    Article  CAS  PubMed  Google Scholar 

  94. Leong, T., Gu, Z., Koh, T. & Gracias, D. H. Spatially controlled chemistry using remotely guided nanoliter scale containers. J. Am. Chem. Soc. 128, 11336–11337 (2006).

    Article  CAS  PubMed  Google Scholar 

  95. Ye, H. et al. Remote radio-frequency controlled nanoliter chemistry and chemical delivery on substrates. Angew. Chem. Int. Ed. 46, 4991–4994 (2007).

    Article  CAS  Google Scholar 

  96. Park, J. R. et al. Reconfigurable microfluidics with metallic containers. J. Microelectromechan. Syst. 17, 265–271 (2008).

    Article  Google Scholar 

  97. Kalinin, Y. V., Randhawa, J. S. & Gracias, D. H. Three-dimensional chemical patterns for cellular self-organization. Angew. Chem. Int. Ed. 50, 2549–2553 (2007).

    Article  CAS  Google Scholar 

  98. Yavuz, M. S. et al. Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat. Mater. 8, 935–939 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Skrabalak, S. E. et al. Gold nanocages: synthesis, properties, and applications. Acc. Chem. Res. 41, 1587–1595 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Sahandi Zangabad, P. et al. Nanocaged platforms: modification, drug delivery and nanotoxicity. opening synthetic cages to release the tiger. Nanoscale 9, 1356–1392 (2017).

    Article  CAS  Google Scholar 

  101. Wang, F., Zhang, Y., Du, Z., Ren, J. & Qu, X. Designed heterogeneous palladium catalysts for reversible light-controlled bioorthogonal catalysis in living cells. Nat. Commun. 9, 1209 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Wang, D., Zhao, W., Wei, Q., Zhao, C. & Zheng, Y. Photoswitchable azobenzene/cyclodextrin host–guest complexes: from UV- to visible/near-IR-light-responsive systems. Chem. Photo. Chem. 2, 403–415 (2018).

    CAS  Google Scholar 

  103. Teh, S.-Y., Lin, R., Hung, L.-H. & Lee, A. P. Droplet microfluidics. Lab. Chip 8, 198–220 (2008).

    Article  CAS  PubMed  Google Scholar 

  104. Gu, H., Duits, M. H. G. & Mugele, F. Droplets formation and merging in two-phase flow microfluidics. Int. J. Mol. Sci. 12, 2572–2597 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Mashaghi, S., Abbaspourrad, A., Weitz, D. A. & van Oijen, A. M. Droplet microfluidics: a tool for biology, chemistry and nanotechnology. TrAC Trends Anal. Chem. 82, 118–125 (2016).

    Article  CAS  Google Scholar 

  106. Thakur, R., Zhang, Y., Amin, A. & Wereley, S. Programmable microfluidic platform for spatiotemporal control over nanoliter droplets. Microfluid. Nanofluidics 18, 1425–1431 (2015).

    Article  Google Scholar 

  107. Tan, W.-H. & Takeuchi, S. Timing controllable electrofusion device for aqueous droplet-based microreactors. Lab. Chip 6, 757–763 (2006).

    Article  CAS  PubMed  Google Scholar 

  108. Yasuga, H. et al. Serial DNA relay in DNA logic gates by electrical fusion and mechanical splitting of droplets. PLOS ONE 12, e0180876 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Bezagu, M. et al. High spatiotemporal control of spontaneous reactions using ultrasound-triggered composite droplets. J. Am. Chem. Soc. 136, 7205–7208 (2014).

    Article  CAS  PubMed  Google Scholar 

  110. Couture, O. et al. Ultrasound internal tattooing. Med. Phys. 38, 1116–1123 (2011).

    Article  PubMed  Google Scholar 

  111. Bezagu, M. et al. In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets. Eur. J. Med. Chem. 142, 2–7 (2017).

    Article  CAS  PubMed  Google Scholar 

  112. Chan, T. G., Morse, S. V., Copping, M. J., Choi, J. J. & Vilar, R. Targeted delivery of DNA–Au nanoparticles across the blood–brain barrier using focused ultrasound. Chem. Med. Chem. 13, 1311–1314 (2018).

    Article  CAS  PubMed  Google Scholar 

  113. Rabe, K. S., Müller, J., Skoupi, M. & Niemeyer, C. M. Cascades in compartments: en route to machine-assisted biotechnology. Angew. Chem. Int. Ed. 56, 13574–13589 (2017).

    Article  CAS  Google Scholar 

  114. Marguet, M., Bonduelle, C. & Lecommandoux, S. Multicompartmentalized polymeric systems: towards biomimetic cellular structure and function. Chem. Soc. Rev. 42, 512–529 (2013).

    Article  CAS  PubMed  Google Scholar 

  115. Rifaie-Graham, O. et al. Wavelength-selective light-responsive DASA-functionalized polymersome nanoreactors. J. Am. Chem. Soc. 140, 8027–8036 (2018).

    Article  CAS  PubMed  Google Scholar 

  116. Grant, J., Modica, J. A., Roll, J., Perkovich, P. & Mrksich, M. An immobilized enzyme reactor for spatiotemporal control over reaction products. Small 14, 1800923 (2018).

  117. Gupta, M. K. et al. 3D printed programmable release capsules. Nano Lett. 15, 5321–5329 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Huang, T.-Y. et al. 3D printed microtransporters: compound micromachines for spatiotemporally controlled delivery of therapeutic agents. Adv. Mater. 27, 6644–6650 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Miyako, E., Chechetka, S. A., Doi, M., Yuba, E. & Kono, K. In vivo remote control of reactions in Caenorhabditis elegans by using supramolecular nanohybrids of carbon nanotubes and liposomes. Angew. Chem. Int. Ed. 54, 9903–9906 (2015).

    Article  CAS  Google Scholar 

  120. Miyako, E. et al. Carbon nanotube–liposome supramolecular nanotrains for intelligent molecular-transport systems. Nat. Commun. 3, 1226 (2012).

    Article  PubMed  CAS  Google Scholar 

  121. Miyako, E. et al. A photo-thermal-electrical converter based on carbon nanotubes for bioelectronic applications. Angew. Chem. Int. Ed. 50, 12266–12270 (2011).

    Article  CAS  Google Scholar 

  122. Chechetka, S. A. et al. Magnetically and near-infrared light-powered supramolecular nanotransporters for the remote control of enzymatic reactions. Angew. Chem. Int. Ed. 55, 6476–6481 (2016).

    Article  CAS  Google Scholar 

  123. Shi, J., Kantoff, P. W., Wooster, R. & Farokhzad, O. C. Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer 17, 20–37 (2017).

    Article  CAS  PubMed  Google Scholar 

  124. Mohamed, S. M., Veeranarayanan, S., Maekawa, T. & Kumar, S. D. External stimulus responsive inorganic nanomaterials for cancer theranostics. Adv. Drug Deliv. Rev. 138, 18–40 (2019).

    Article  CAS  Google Scholar 

  125. Chechetka, S. A. et al. Light-driven liquid metal nanotransformers for biomedical theranostics. Nat. Commun. 8, 15432 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Yu, Y. et al. Self-assembled nanodiamond supraparticles for anticancer chemotherapy. Nanoscale 10, 8969–8978 (2018).

    Article  CAS  PubMed  Google Scholar 

  127. Barner-Kowollik, C. et al. 3D laser micro- and nanoprinting: challenges for chemistry. Angew. Chem. Int. Ed. 56, 15828–15845 (2017).

    Article  CAS  Google Scholar 

  128. Hippler, M. et al. 3D scaffolds to study basic cell biology. Adv. Mater. 31, 1808110 (2019).

    Article  CAS  Google Scholar 

  129. Melissinaki, V. et al. Direct laser writing of 3D scaffolds for neural tissue engineering applications. Biofabrication 3, 045005 (2011).

    Article  CAS  PubMed  Google Scholar 

  130. Gregor, A. et al. Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer. J. Biol. Eng. 11, 31 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Hell, S. W. & Wichmann, J. Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. Opt. Lett. 19, 780–782 (1994).

    Article  CAS  PubMed  Google Scholar 

  132. Bialas, S. et al. Access to disparate soft matter materials by curing with two colors of light. Adv. Mater. 31, 1807288 (2019).

    Article  CAS  Google Scholar 

  133. Frisch, H., Bloesser, F. R. & Barner-Kowollik, C. Controlling chain coupling and single-chain ligation by two colours of visible light. Angew. Chem. Int. Ed. 58, 3604–3609 (2019).

    Article  CAS  Google Scholar 

  134. Menzel, J. P. et al. Light-controlled orthogonal covalent bond formation at two different wavelengths. Angew. Chem. Int. Ed. 58, 7470–7474 (2019).

    Article  CAS  Google Scholar 

  135. Qin, X.-H., Wang, X., Rottmar, M., Nelson, B. J. & Maniura-Weber, K. Near-infrared light-sensitive polyvinyl alcohol hydrogel photoresist for spatiotemporal control of cell-instructive 3D microenvironments. Adv. Mater. 30, 1705564 (2018).

    Article  CAS  Google Scholar 

  136. Gernhardt, M. et al. Tailoring the mechanical properties of 3D microstructures using visible light post-manufacturing. Adv. Mater. 31, e1901269 (2019).

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Acknowledgements

The authors thank Queen Mary University of London and L’Oréal Unesco for Women in Science for funding.

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Aubert, S., Bezagu, M., Spivey, A.C. et al. Spatial and temporal control of chemical processes. Nat Rev Chem 3, 706–722 (2019). https://doi.org/10.1038/s41570-019-0139-6

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