Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Responsive biomaterials: optimizing control of cancer immunotherapy

Nature Reviews Materials volume 9, pages 100–118 (2024)Cite this article

Subjects

Abstract

Immunotherapy has emerged as an eminent and effective modality in the treatment of cancer. However, current cancer immunotherapies lack spatial and temporal control, resulting in systemic side effects and suboptimal patient outcomes. Responsive biomaterials have proven to be powerful tools for controlling cancer immunotherapies by providing precise control over the delivery and kinetics of immunotherapeutic cargoes. Here, we discuss biological barriers to cancer immunotherapy and how biomaterial-based strategies that respond to different stimuli — both internal and external — can be used to increase the therapeutic efficacy while reducing the toxicity of cancer immunotherapies. We examine the use of biomaterials that respond to physiological stimuli (pH, enzymes and redox potential) and exogenous energetic stimuli (light, magnetism and ultrasound) and expand upon the use of these strategies in propagating three key approaches in cancer immunotherapy: cancer vaccines, T cell-based therapy and therapies involving sustained delivery.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Developments in cancer immunotherapy.
Fig. 2: Biomaterials responsive to endogenous stimuli for cancer immunotherapy.
Fig. 3: Key biological barriers for cancer immunotherapy.
Fig. 4: Biomaterials incorporated with exogeneous stimuli for boosting cancer immunotherapy.
Fig. 5: Approaches benefitting from biomaterial-based intervention to bolster cancer immunotherapy.

Similar content being viewed by others

References

  1. Zhu, Y. et al. STING: a master regulator in the cancer-immunity cycle. Mol. Cancer 18, 152 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Garland, K. M., Sheehy, T. L. & Wilson, J. T. Chemical and biomolecular strategies for STING pathway activation in cancer immunotherapy. Chem. Rev. 122, 5977–6039 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lesterhuis, W. J., Haanen, J. B. A. G. & Punt, C. J. A. Cancer immunotherapy — revisited. Nat. Rev. Drug Discov. 10, 591–600 (2011).

    Article  CAS  PubMed  Google Scholar 

  4. Tanaka, A. & Sakaguchi, S. Regulatory T cells in cancer immunotherapy. Cell Res. 27, 109–118 (2017).

    Article  CAS  PubMed  Google Scholar 

  5. Colombo, M. P. & Piconese, S. Regulatory T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat. Rev. Cancer 7, 880–887 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Nishikawa, H. & Sakaguchi, S. Regulatory T cells in cancer immunotherapy. Curr. Opin. Immunol. 27, 1–7 (2014).

    Article  CAS  PubMed  Google Scholar 

  7. Gong, N., Sheppard, N. C., Billingsley, M. M., June, C. H. & Mitchell, M. J. Nanomaterials for T-cell cancer immunotherapy. Nat. Nanotechnol. 16, 25–36 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Jackson, H. J., Rafiq, S. & Brentjens, R. J. Driving CAR T-cells forward. Nat. Rev. Clin. Oncol. 13, 370–383 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. June, C. H., O’Connor, R. S., Kawalekar, O. U., Ghassemi, S. & Milone, M. C. CAR T cell immunotherapy for human cancer. Science 359, 1361–1365 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Shah, N. N. & Fry, T. J. Mechanisms of resistance to CAR T cell therapy. Nat. Rev. Clin. Oncol. 16, 372–385 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Mellman, I., Coukos, G. & Dranoff, G. Cancer immunotherapy comes of age. Nature 480, 480–489 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  12. Chabner, B. A. & Roberts, T. G. Chemotherapy and the war on cancer. Nat. Rev. Cancer 5, 65–72 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Blattman, J. N. & Greenberg, P. D. Cancer immunotherapy: a treatment for the masses. Science 305, 200–205 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Javier, R. T. & Butel, J. S. The history of tumor virology. Cancer Res. 68, 7693–7706 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Topalian, S. L., Drake, C. G. & Pardoll, D. M. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27, 450–461 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wei, S. C., Duffy, C. R. & Allison, J. P. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 8, 1069–1086 (2018).

    Article  PubMed  Google Scholar 

  17. Ledford, H., Else, H. & Warren, M. Cancer immunologists scoop medicine Nobel Prize. Nature 562, 20–21 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Fedorov, V. D., Themeli, M. & Sadelain, M. PD-1- and CTLA-4-based Inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci. Transl Med. 5, 215ra172 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Zitvogel, L., Rusakiewicz, S., Routy, B., Ayyoub, M. & Kroemer, G. Immunological off-target effects of imatinib. Nat. Rev. Clin. Oncol. 13, 431–446 (2016).

    Article  CAS  PubMed  Google Scholar 

  20. Irvine, D. J. & Dane, E. L. Enhancing cancer immunotherapy with nanomedicine. Nat. Rev. Immunol. 20, 321–334 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Martin, J. D., Cabral, H., Stylianopoulos, T. & Jain, R. K. Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges. Nat. Rev. Clin. Oncol. 17, 251–266 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Riley, R. S., June, C. H., Langer, R. & Mitchell, M. J. Delivery technologies for cancer immunotherapy. Nat. Rev. Drug Discov. 18, 175–196 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chao, Y. & Liu, Z. Biomaterials tools to modulate the tumour microenvironment in immunotherapy. Nat. Rev. Bioeng. 1, 125–138 (2023).

    Article  Google Scholar 

  24. Bo, Y. & Wang, H. Biomaterial‐based in situ cancer vaccines. Adv. Mater. 17, e2210452 (2023).

    Article  Google Scholar 

  25. Huang, P. et al. Nano-, micro-, and macroscale drug delivery systems for cancer immunotherapy. Acta Biomater. 85, 1–26 (2019).

    Article  CAS  PubMed  Google Scholar 

  26. Viswanath, D. I., Liu, H.-C., Huston, D. P., Chua, C. Y. X. & Grattoni, A. Emerging biomaterial-based strategies for personalized therapeutic in situ cancer vaccines. Biomaterials 280, 121297 (2022).

    Article  CAS  PubMed  Google Scholar 

  27. Weber, J. S. & Mulé, J. J. Cancer immunotherapy meets biomaterials. Nat. Biotechnol. 33, 44–45 (2015).

    Article  CAS  PubMed  Google Scholar 

  28. Yan, S. et al. Improving cancer immunotherapy outcomes using biomaterials. Angew. Chem. Int. Ed. 132, 17484–17495 (2020).

    Article  ADS  Google Scholar 

  29. Curvello, R., Kast, V., Ordóñez-Morán, P., Mata, A. & Loessner, D. Biomaterial-based platforms for tumour tissue engineering. Nat. Rev. Mater. 8, 314–330 (2023).

    Article  ADS  CAS  Google Scholar 

  30. De Angelis, B. et al. Stimuli-responsive nanoparticle-assisted immunotherapy: a new weapon against solid tumours. J. Mater. Chem. B 8, 1823–1840 (2020).

    Article  PubMed  Google Scholar 

  31. Li, L., Yang, Z. & Chen, X. Recent advances in stimuli-responsive platforms for cancer immunotherapy. Acc. Chem. Res. 53, 2044–2054 (2020).

    Article  CAS  PubMed  Google Scholar 

  32. Pacifici, N., Bolandparvaz, A. & Lewis, J. S. Stimuli‐responsive biomaterials for vaccines and immunotherapeutic applications. Adv. Ther. 3, 2000129 (2020).

    Article  Google Scholar 

  33. Qin, J. et al. Stimuli-responsive hydrogels for cancer immunotherapy. Polym. Chem. 14, 793–802 (2023).

    Article  CAS  Google Scholar 

  34. Zhao, Y., Guo, Y. & Tang, L. Engineering cancer vaccines using stimuli-responsive biomaterials. Nano Res. 11, 5355–5371 (2018).

    Article  CAS  Google Scholar 

  35. Lu, Y., Aimetti, A. A., Langer, R. & Gu, Z. Bioresponsive materials. Nat. Rev. Mater. 2, 16075 (2016).

    Article  ADS  Google Scholar 

  36. Mahoney, K. M., Rennert, P. D. & Freeman, G. J. Combination cancer immunotherapy and new immunomodulatory targets. Nat. Rev. Drug Discov. 14, 561–584 (2015).

    Article  CAS  PubMed  Google Scholar 

  37. Nam, J. et al. Cancer nanomedicine for combination cancer immunotherapy. Nat. Rev. Mater. 4, 398–414 (2019).

    Article  ADS  Google Scholar 

  38. Sang, W., Zhang, Z., Dai, Y. & Chen, X. Recent advances in nanomaterial-based synergistic combination cancer immunotherapy. Chem. Soc. Rev. 48, 3771–3810 (2019).

    Article  PubMed  Google Scholar 

  39. Smyth, M. J., Ngiow, S. F., Ribas, A. & Teng, M. W. L. Combination cancer immunotherapies tailored to the tumour microenvironment. Nat. Rev. Clin. Oncol. 13, 143–158 (2016).

    Article  CAS  PubMed  Google Scholar 

  40. Quail, D. F. & Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19, 1423–1437 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Finger, E. C. & Giaccia, A. J. Hypoxia, inflammation, and the tumor microenvironment in metastatic disease. Cancer Metastasis Rev. 29, 285–293 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tsai, M.-J., Chang, W.-A., Huang, M.-S. & Kuo, P.-L. Tumor microenvironment: a new treatment target for cancer. ISRN Biochem. 2014, 1–8 (2014).

    Article  Google Scholar 

  43. Yang, M., Li, J., Gu, P. & Fan, X. The application of nanoparticles in cancer immunotherapy: targeting tumor microenvironment. Bioact. Mater. 6, 1973–1987 (2021).

    CAS  PubMed  Google Scholar 

  44. Peng, S., Xiao, F., Chen, M. & Gao, H. Tumor‐microenvironment‐responsive nanomedicine for enhanced cancer immunotherapy. Adv. Sci. 9, 2103836 (2022).

    Article  CAS  Google Scholar 

  45. Manchun, S., Dass, C. R. & Sriamornsak, P. Targeted therapy for cancer using pH-responsive nanocarrier systems. Life Sci. 90, 381–387 (2012).

    Article  CAS  PubMed  Google Scholar 

  46. Yan, Y. & Ding, H. pH-responsive nanoparticles for cancer immunotherapy: a brief review. Nanomaterials 10, 1613 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li, Z., Huang, J. & Wu, J. pH-sensitive nanogels for drug delivery in cancer therapy. Biomater. Sci. 9, 574–589 (2021).

    Article  CAS  PubMed  Google Scholar 

  48. Zhou, T. et al. A nanogel of on-site tunable pH-response for efficient anticancer drug delivery. Acta Biomater. 9, 4546–4557 (2013).

    Article  CAS  PubMed  Google Scholar 

  49. Oberli, M. A. et al. Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 17, 1326–1335 (2017).

    Article  ADS  CAS  PubMed  Google Scholar 

  50. Gu, Z., Da Silva, C., Van Der Maaden, K., Ossendorp, F. & Cruz, L. Liposome-based drug delivery systems in cancer immunotherapy. Pharmaceutics 12, 1054 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Trimaille, T., Lacroix, C. & Verrier, B. Self-assembled amphiphilic copolymers as dual delivery system for immunotherapy. Eur. J. Pharm. Biopharm. 142, 232–239 (2019).

    Article  CAS  PubMed  Google Scholar 

  52. Zhu, G., Zhang, F., Ni, Q., Niu, G. & Chen, X. Efficient nanovaccine delivery in cancer immunotherapy. ACS Nano 11, 2387–2392 (2017).

    Article  CAS  PubMed  Google Scholar 

  53. Ma, X. et al. Bioengineered nanogels for cancer immunotherapy. Chem. Soc. Rev. 51, 5136–5174 (2022).

    Article  CAS  PubMed  Google Scholar 

  54. Guo, R.-C. et al. Recent progress of therapeutic peptide based nanomaterials: from synthesis and self-assembly to cancer treatment. Biomater. Sci. 8, 6175–6189 (2020).

    Article  CAS  PubMed  Google Scholar 

  55. Ni, K., Luo, T., Nash, G. T. & Lin, W. Nanoscale metal–organic frameworks for cancer immunotherapy. Acc. Chem. Res. 53, 1739–1748 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Alsaiari, S. K. et al. Sustained and targeted delivery of checkpoint inhibitors by metal–organic frameworks for cancer immunotherapy. Sci. Adv. 7, eabe7174 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  57. Li, J. et al. Hybrid nanomaterials for cancer immunotherapy. Adv. Sci. 10, 2204932 (2023).

    Article  ADS  CAS  Google Scholar 

  58. Wang, C., Ye, Y., Hu, Q., Bellotti, A. & Gu, Z. Tailoring biomaterials for cancer immunotherapy: emerging trends and future outlook. Adv. Mater. 29, 1606036 (2017).

    Article  Google Scholar 

  59. Nuhn, L. et al. pH-degradable imidazoquinoline-ligated nanogels for lymph node-focused immune activation. Proc. Natl Acad. Sci. USA 113, 8098–8103 (2016).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  60. Jacobson, M. E., Wang-Bishop, L., Becker, K. W. & Wilson, J. T. Delivery of 5′-triphosphate RNA with endosomolytic nanoparticles potently activates RIG-I to improve cancer immunotherapy. Biomater. Sci. 7, 547–559 (2019).

    Article  CAS  PubMed  Google Scholar 

  61. Shae, D. et al. Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy. Nat. Nanotechnol. 14, 269–278 (2019).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  62. Luo, M. et al. A STING-activating nanovaccine for cancer immunotherapy. Nat. Nanotechnol. 12, 648–654 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  63. Li, S. et al. Prolonged activation of innate immune pathways by a polyvalent STING agonist. Nat. Biomed. Eng. 5, 455–466 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ahmad, A., Khan, J. M. & Haque, S. Strategies in the design of endosomolytic agents for facilitating endosomal escape in nanoparticles. Biochimie 160, 61–75 (2019).

    Article  CAS  PubMed  Google Scholar 

  65. Marušič, N. et al. Increased efficiency of charge-mediated fusion in polymer/lipid hybrid membranes. Proc. Natl Acad. Sci. USA 119, e2122468119 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Yuba, E., Harada, A., Sakanishi, Y., Watarai, S. & Kono, K. A liposome-based antigen delivery system using pH-sensitive fusogenic polymers for cancer immunotherapy. Biomaterials 34, 3042–3052 (2013).

    Article  CAS  PubMed  Google Scholar 

  67. Kunisawa, J. et al. Sendai virus fusion protein-mediates simultaneous induction of MHC class I/II-dependent mucosal and systemic immune responses via the nasopharyngeal-associated lymphoreticular tissue immune system. J. Immunol. 167, 1406–1412 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Yavlovich, A., Smith, B., Gupta, K., Blumenthal, R. & Puri, A. Light-sensitive lipid-based nanoparticles for drug delivery: design principles and future considerations for biological applications. Mol. Membr. Biol. 27, 364–381 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Zong, Y., Lin, Y., Wei, T. & Cheng, Q. Lipid nanoparticle (LNP) enables mRNA delivery for cancer therapy. Adv. Mater. https://doi.org/10.1002/adma.202303261 (2023).

  70. Huang, T. et al. Lipid nanoparticle-based mRNA vaccines in cancers: current advances and future prospects. Front. Immunol. 13, 922301 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Liu, C. et al. mRNA-based cancer therapeutics. Nat. Rev. Cancer 23, 526–543 (2023).

    Article  PubMed  Google Scholar 

  72. Zhang, H. et al. Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through Toll-like receptor 4 signaling. Proc. Natl Acad. Sci. USA 118, e2005191118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Miao, L. et al. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat. Biotechnol. 37, 1174–1185 (2019).

    Article  CAS  PubMed  Google Scholar 

  74. Islam, M. A. et al. Adjuvant-pulsed mRNA vaccine nanoparticle for immunoprophylactic and therapeutic tumor suppression in mice. Biomaterials 266, 120431 (2021).

    Article  CAS  PubMed  Google Scholar 

  75. Lee, K. et al. Adjuvant incorporated lipid nanoparticles for enhanced mRNA-mediated cancer immunotherapy. Biomater. Sci. 8, 1101–1105 (2020).

    Article  CAS  PubMed  Google Scholar 

  76. Yan, J. et al. Nanomaterials‐mediated co‐stimulation of toll‐like receptors and CD40 for antitumor immunity. Adv. Mater. 34, 2207486 (2022).

    Article  CAS  Google Scholar 

  77. Chen, Q. et al. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat. Nanotechnol. 14, 89–97 (2019).

    Article  ADS  CAS  PubMed  Google Scholar 

  78. Huppertsberg, A. et al. Squaric ester-based, pH-degradable nanogels: modular nanocarriers for safe, systemic administration of toll-like receptor 7/8 agonistic immune modulators. J. Am. Chem. Soc. 143, 9872–9883 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Li, D. et al. Progress and perspective of microneedle system for anti-cancer drug delivery. Biomaterials 264, 120410 (2021).

    Article  CAS  PubMed  Google Scholar 

  80. Wang, C., Ye, Y., Hochu, G. M., Sadeghifar, H. & Gu, Z. Enhanced cancer immunotherapy by microneedle patch-assisted delivery of anti-PD1 antibody. Nano Lett. 16, 2334–2340 (2016).

    Article  ADS  CAS  PubMed  Google Scholar 

  81. Duong, H. T. T. et al. Smart vaccine delivery based on microneedle arrays decorated with ultra-pH-responsive copolymers for cancer immunotherapy. Biomaterials 185, 13–24 (2018).

    Article  CAS  PubMed  Google Scholar 

  82. Li, M., Zhao, G., Su, W.-K. & Shuai, Q. Enzyme-responsive nanoparticles for anti-tumor drug delivery. Front. Chem. 8, 647 (2020).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  83. Shahriari, M. et al. Enzyme responsive drug delivery systems in cancer treatment. J. Control. Release 308, 172–189 (2019).

    Article  CAS  PubMed  Google Scholar 

  84. Wang, D. et al. Engineering nanoparticles to locally activate T cells in the tumor microenvironment. Sci. Immunol. 4, eaau6584 (2019).

    Article  CAS  PubMed  Google Scholar 

  85. Xing, F. Cancer associated fibroblasts (CAFs) in tumor microenvironment. Front. Biosci. 15, 166 (2010).

    Article  CAS  PubMed Central  Google Scholar 

  86. Ji, T. et al. Transformable peptide nanocarriers for expeditious drug release and effective cancer therapy via cancer-associated fibroblast activation. Angew. Chem. Int. Ed. 55, 1050–1055 (2016).

    Article  CAS  Google Scholar 

  87. Sun, M. et al. Fibroblast activation protein‐α responsive peptide assembling prodrug nanoparticles for remodeling the immunosuppressive microenvironment and boosting cancer immunotherapy. Small 18, 2106296 (2022).

    Article  CAS  Google Scholar 

  88. Wei, L., Zhao, Y., Hu, X. & Tang, L. Redox-responsive polycondensate neoepitope for enhanced personalized cancer vaccine. ACS Cent. Sci. 6, 404–412 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Estrela, J. M., Ortega, A. & Obrador, E. Glutathione in cancer biology and therapy. Crit. Rev. Clin. Lab. Sci. 43, 143–181 (2006).

    Article  CAS  PubMed  Google Scholar 

  90. Li, L. et al. Burst release of encapsulated annexin A5 in tumours boosts cytotoxic T-cell responses by blocking the phagocytosis of apoptotic cells. Nat. Biomed. Eng. 4, 1102–1116 (2020).

    Article  CAS  PubMed  Google Scholar 

  91. Wang, N. et al. Vaccination of TLR7/8 agonist‐conjugated antigen nanoparticles for cancer immunotherapy. Adv. Healthc. Mater. 4, e2300249 (2023).

    Article  Google Scholar 

  92. Kuai, R., Ochyl, L. J., Bahjat, K. S., Schwendeman, A. & Moon, J. J. Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat. Mater. 16, 489–496 (2017).

    Article  ADS  CAS  PubMed  Google Scholar 

  93. Lv, M. et al. Redox-responsive hyperbranched poly(amido amine) and polymer dots as a vaccine delivery system for cancer immunotherapy. J. Mater. Chem. B 5, 9532–9545 (2017).

    Article  CAS  PubMed  Google Scholar 

  94. Yang, B., Gao, J., Pei, Q., Xu, H. & Yu, H. Engineering prodrug nanomedicine for cancer immunotherapy. Adv. Sci. 7, 2002365 (2020).

    Article  CAS  Google Scholar 

  95. Qian, S. et al. IDO as a drug target for cancer immunotherapy: recent developments in IDO inhibitors discovery. RSC Adv. 6, 7575–7581 (2016).

    Article  ADS  CAS  Google Scholar 

  96. Yan, P. et al. A redox‐responsive nanovaccine combined with a2a receptor antagonist for cancer immunotherapy. Adv. Healthc. Mater. 10, 2101222 (2021).

    Article  CAS  Google Scholar 

  97. Wang, K.-S. et al. A redox-responsive prodrug nanogel of TLR7/8 agonist for improved cancer immunotherapy. Chinese J. Polym. Sci. 41, 32–39 (2023).

    Article  Google Scholar 

  98. Mi, Y. et al. Abstract 2866: neoantigen nanovaccine improves personalized cancer immunotherapy. Cancer Res. 80, 2866–2866 (2020).

    Article  Google Scholar 

  99. Ben-Akiva, E. et al. Biodegradable lipophilic polymeric mRNA nanoparticles for ligand-free targeting of splenic dendritic cells for cancer vaccination. Proc. Natl Acad. Sci. USA 120, e2301606120 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Chen, J. et al. Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8 + T cell response. Proc. Natl Acad. Sci. USA 119, e2207841119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Wang, F. et al. Tumour sensitization via the extended intratumoural release of a STING agonist and camptothecin from a self-assembled hydrogel. Nat. Biomed. Eng. 4, 1090–1101 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Yang, Y. & Sun, W. Recent advances in redox-responsive nanoparticles for combined cancer therapy. Nanoscale Adv. 4, 3504–3516 (2022).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  103. Li, D., Zhang, R., Liu, G., Kang, Y. & Wu, J. Redox‐responsive self‐assembled nanoparticles for cancer therapy. Adv. Healthc. Mater. 9, 2000605 (2020).

    Article  CAS  Google Scholar 

  104. Jeong, S., Choi, Y. & Kim, K. Engineering therapeutic strategies in cancer immunotherapy via exogenous delivery of toll-like receptor agonists. Pharmaceutics 13, 1374 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kang, W., Liu, Y. & Wang, W. Light-responsive nanomedicine for cancer immunotherapy. Acta Pharm. Sin. B 13, 2346–2368 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Day, N. B., Wixson, W. C. & Shields, C. W. Magnetic systems for cancer immunotherapy. Acta Pharm. Sin. B 11, 2172–2196 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Unga, J. & Hashida, M. Ultrasound induced cancer immunotherapy. Adv. Drug Deliv. Rev. 72, 144–153 (2014).

    Article  CAS  PubMed  Google Scholar 

  108. Chen, H. & Zhao, Y. Applications of light-responsive systems for cancer theranostics. ACS Appl. Mater. Interfaces 10, 21021–21034 (2018).

    Article  CAS  PubMed  Google Scholar 

  109. Wang, X., Xiao, X., Feng, Y., Li, J. & Zhang, Y. A photoresponsive antibody–siRNA conjugate for activatable immunogene therapy of cancer. Chem. Sci. 13, 5345–5352 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Song, Y., Chen, Y., Li, P. & Dong, C.-M. Photoresponsive polypeptide-glycosylated dendron amphiphiles: UV-triggered polymersomes, OVA release, and in vitro enhanced uptake and immune response. Biomacromolecules 21, 5345–5357 (2020).

    Article  CAS  PubMed  Google Scholar 

  111. Yang, G., Liu, J., Wu, Y., Feng, L. & Liu, Z. Near-infrared-light responsive nanoscale drug delivery systems for cancer treatment. Coord. Chem. Rev. 320–321, 100–117 (2016).

    Article  Google Scholar 

  112. Chu, H., Zhao, J., Mi, Y., Di, Z. & Li, L. NIR-light-mediated spatially selective triggering of anti-tumor immunity via upconversion nanoparticle-based immunodevices. Nat. Commun. 10, 2839 (2019).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  113. Chen, G., Qiu, H., Prasad, P. N. & Chen, X. Upconversion nanoparticles: design, nanochemistry, and applications in theranostics. Chem. Rev. 114, 5161–5214 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Liu, Y., Meng, X. & Bu, W. Upconversion-based photodynamic cancer therapy. Coord. Chem. Rev. 379, 82–98 (2019).

    Article  CAS  Google Scholar 

  115. Tian, G., Zhang, X., Gu, Z. & Zhao, Y. Recent advances in upconversion nanoparticles-based multifunctional nanocomposites for combined cancer therapy. Adv. Mater. 27, 7692–7712 (2015).

    Article  CAS  PubMed  Google Scholar 

  116. Wang, C., Cheng, L. & Liu, Z. Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. Biomaterials 32, 1110–1120 (2011).

    Article  CAS  PubMed  Google Scholar 

  117. Lee, H. P. & Gaharwar, A. K. Light‐responsive inorganic biomaterials for biomedical applications. Adv. Sci. 7, 2000863 (2020).

    Article  CAS  Google Scholar 

  118. Zhang, X., Wang, S., Cheng, G., Yu, P. & Chang, J. Light-responsive nanomaterials for cancer therapy. Engineering 13, 18–30 (2022).

    Article  CAS  Google Scholar 

  119. Yan, B. et al. Engineering magnetic nano-manipulators for boosting cancer immunotherapy. J. Nanobiotechnol. 20, 547 (2022).

    Article  CAS  Google Scholar 

  120. Li, K., Nejadnik, H. & Daldrup-Link, H. E. Next-generation superparamagnetic iron oxide nanoparticles for cancer theranostics. Drug Discov. Today 22, 1421–1429 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Ito, A., Honda, H. & Kobayashi, T. Cancer immunotherapy based on intracellular hyperthermia using magnetite nanoparticles: a novel concept of ‘heat-controlled necrosis’ with heat shock protein expression. Cancer Immunol. Immunother. 55, 320–328 (2006).

    Article  CAS  PubMed  Google Scholar 

  122. Ksienski, D. et al. Pembrolizumab for advanced nonsmall cell lung cancer: efficacy and safety in everyday clinical practice. Lung Cancer 133, 110–116 (2019).

    Article  PubMed  Google Scholar 

  123. Chen, Q. et al. Novel targeted pH-responsive drug delivery systems based on PEGMA-modified bimetallic Prussian blue analogs for breast cancer chemotherapy. RSC Adv. 13, 1684–1700 (2023).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  124. Morrow, M., Waters, J. & Morris, E. MRI for breast cancer screening, diagnosis, and treatment. Lancet 378, 1804–1811 (2011).

    Article  PubMed  Google Scholar 

  125. Li, T. et al. Bioinspired magnetic nanocomplexes amplifying STING activation of tumor-associated macrophages to potentiate cancer immunotherapy. Nano Today 43, 101400 (2022).

    Article  CAS  Google Scholar 

  126. Chiang, C.-S. et al. Combination of fucoidan-based magnetic nanoparticles and immunomodulators enhances tumour-localized immunotherapy. Nat. Nanotechnol. 13, 746–754 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  127. Mejías, R. et al. Dimercaptosuccinic acid-coated magnetite nanoparticles for magnetically guided in vivo delivery of interferon gamma for cancer immunotherapy. Biomaterials 32, 2938–2952 (2011).

    Article  PubMed  Google Scholar 

  128. Zhu, J., Wang, J. & Li, Y. Recent advances in magnetic nanocarriers for tumor treatment. Biomed. Pharmacother. 159, 114227 (2023).

    Article  CAS  PubMed  Google Scholar 

  129. Sharma, D., Leong, K. X. & Czarnota, G. J. Application of ultrasound combined with microbubbles for cancer therapy. Int. J. Mol. Sci. 23, 4393 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Tu, J., Zhang, H., Yu, J., Liufu, C. & Chen, Z. Ultrasound-mediated microbubble destruction: a new method in cancer immunotherapy. Onco Targets Ther. 11, 5763–5775 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Wang, S., Hu, X., Wei, W. & Ma, G. Transformable vesicles for cancer immunotherapy. Adv. Drug Deliv. Rev. 179, 113905 (2021).

    Article  CAS  PubMed  Google Scholar 

  132. Seo, H. S., Wang, C.-P. J., Park, W. & Park, C. G. Short review on advances in hydrogel-based drug delivery strategies for cancer immunotherapy. Tissue Eng. Regen. Med. 19, 263–280 (2022).

    Article  CAS  PubMed  Google Scholar 

  133. Li, X. et al. Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles. Nat. Nanotechnol. 17, 891–899 (2022).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  134. Meng, Z. et al. Ultrasound-mediated remotely controlled nanovaccine delivery for tumor vaccination and individualized cancer immunotherapy. Nano Lett. 21, 1228–1237 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  135. Zhou, L.-Q., Li, P., Cui, X.-W. & Dietrich, C. F. Ultrasound nanotheranostics in fighting cancer: advances and prospects. Cancer Lett. 470, 204–219 (2020).

    Article  CAS  PubMed  Google Scholar 

  136. Zhang, N., Wang, J., Foiret, J., Dai, Z. & Ferrara, K. W. Synergies between therapeutic ultrasound, gene therapy and immunotherapy in cancer treatment. Adv. Drug Deliv. Rev. 178, 113906 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Saxena, M., Van Der Burg, S. H., Melief, C. J. M. & Bhardwaj, N. Therapeutic cancer vaccines. Nat. Rev. Cancer 21, 360–378 (2021).

    Article  CAS  PubMed  Google Scholar 

  138. Sahin, U. & Türeci, Ö. Personalized vaccines for cancer immunotherapy. Science 359, 1355–1360 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  139. Finn, O. J. Cancer vaccines: between the idea and the reality. Nat. Rev. Immunol. 3, 630–641 (2003).

    Article  CAS  PubMed  Google Scholar 

  140. Duong, H. T. T. et al. Microneedle arrays coated with charge reversal pH-sensitive copolymers improve antigen presenting cells-homing DNA vaccine delivery and immune responses. J. Control. Release 269, 225–234 (2018).

    Article  CAS  PubMed  Google Scholar 

  141. Liu, K. et al. A novel multifunctional vaccine platform with dendritic cell-targeting and pH-responsive for cancer immunotherapy: antigen-directed biomimetic fabrication of a cabbage-like mannatide-zinc-antigen hybrid microparticles. Chem. Eng. J. 426, 130867 (2021).

    Article  CAS  Google Scholar 

  142. Shih, T.-Y., Najibi, A. J., Bartlett, A. L., Li, A. W. & Mooney, D. J. Ultrasound-triggered release reveals optimal timing of CpG-ODN delivery from a cryogel cancer vaccine. Biomaterials 279, 121240 (2021).

    Article  CAS  PubMed  Google Scholar 

  143. Vasdekis, A. E., Scott, E. A., O’Neil, C. P., Psaltis, D. & Hubbell, J. A. Precision intracellular delivery based on optofluidic polymersome rupture. ACS Nano 6, 7850–7857 (2012).

    Article  CAS  PubMed  Google Scholar 

  144. Gao, Y., Zhao, Q., Xiao, M., Huang, X. & Wu, X. A versatile photothermal vaccine based on acid-responsive glyco-nanoplatform for synergistic therapy of cancer. Biomaterials 273, 120792 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Ni, Q. et al. Nanomaterials with changeable physicochemical property for boosting cancer immunotherapy. J. Control. Release 342, 210–227 (2022).

    Article  CAS  PubMed  Google Scholar 

  146. Wang, J. et al. In situ phase transitional polymeric vaccines for improved immunotherapy. Natl Sci. Rev. 9, nwab159 (2022).

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  147. Liu, S. et al. A DNA nanodevice-based vaccine for cancer immunotherapy. Nat. Mater. 20, 421–430 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  148. Reddy, S. T. et al. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat. Biotechnol. 25, 1159–1164 (2007).

    Article  CAS  PubMed  Google Scholar 

  149. Wang, Y. et al. In situ manipulation of dendritic cells by an autophagy-regulative nanoactivator enables effective cancer immunotherapy. ACS Nano 13, 7568–7577 (2019).

    Article  CAS  PubMed  Google Scholar 

  150. Ghiringhelli, F. et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors. Nat. Med. 15, 1170–1178 (2009).

    Article  CAS  PubMed  Google Scholar 

  151. Gong, N. et al. Proton-driven transformable nanovaccine for cancer immunotherapy. Nat. Nanotechnol. 15, 1053–1064 (2020).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  152. Xia, Y. et al. Exploiting the pliability and lateral mobility of Pickering emulsion for enhanced vaccination. Nat. Mater. 17, 187–194 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

  153. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646–674 (2011).

    Article  CAS  PubMed  Google Scholar 

  154. Mai, D., June, C. H. & Sheppard, N. C. In vivo gene immunotherapy for cancer. Sci. Transl Med. 14, eabo3603 (2022).

    Article  CAS  PubMed  Google Scholar 

  155. Zhu, G. et al. Intertwining DNA–RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy. Nat. Commun. 8, 1482 (2017).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  156. Khattak, A. et al. Abstract CT001: a personalized cancer vaccine, mRNA-4157, combined with pembrolizumab versus pembrolizumab in patients with resected high-risk melanoma: efficacy and safety results from the randomized, open-label phase 2 mRNA-4157-P201/Keynote-942 trial. Cancer Res. 83, CT001 (2023).

    Article  Google Scholar 

  157. Rosenberg, S. A., Restifo, N. P., Yang, J. C., Morgan, R. A. & Dudley, M. E. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat. Rev. Cancer 8, 299–308 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Farhood, B., Najafi, M. & Mortezaee, K. CD8+ cytotoxic T lymphocytes in cancer immunotherapy: a review. J. Cell. Physiol. 234, 8509–8521 (2019).

    Article  CAS  PubMed  Google Scholar 

  159. Li, D. et al. Genetically engineered T cells for cancer immunotherapy. Signal Transduct. Target. Ther. 4, 35 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Miliotou, A. N. & Papadopoulou, L. C. CAR T-cell therapy: a new era in cancer immunotherapy. Curr. Pharm. Biotechnol. 19, 5–18 (2018).

    Article  PubMed  Google Scholar 

  161. Chen, Y.-J., Abila, B. & Mostafa Kamel, Y. CAR-T: what is next? Cancers 15, 663 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Liu, Y., Sperling, A. S., Smith, E. L. & Mooney, D. J. Optimizing the manufacturing and antitumour response of CAR T therapy. Nat. Rev. Bioeng. 1, 271–285 (2023).

    Article  Google Scholar 

  163. Perica, K. et al. Magnetic field-induced T cell receptor clustering by nanoparticles enhances T cell activation and stimulates antitumor activity. ACS Nano 8, 2252–2260 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Smith, T. T. et al. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nat. Nanotechnol. 12, 813–820 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Moffett, H. F. et al. Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers. Nat. Commun. 8, 389 (2017).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  166. Dunn, Z. S., Mac, J. & Wang, P. T cell immunotherapy enhanced by designer biomaterials. Biomaterials 217, 119265 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Tang, L. et al. Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery. Nat. Biotechnol. 36, 707–716 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Shang, Q. et al. Local scaffold-assisted delivery of immunotherapeutic agents for improved cancer immunotherapy. Adv. Drug Deliv. Rev. 185, 114308 (2022).

    Article  CAS  PubMed  Google Scholar 

  169. Abdou, P. et al. Advances in engineering local drug delivery systems for cancer immunotherapy. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 12, e1632 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  170. Li, J. et al. Implantable and injectable biomaterial scaffolds for cancer immunotherapy. Front. Bioeng. Biotechnol. 8, 612950 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Leach, D. G., Young, S. & Hartgerink, J. D. Advances in immunotherapy delivery from implantable and injectable biomaterials. Acta Biomater. 88, 15–31 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Lu, X. et al. Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy. Sci. Transl Med. 12, eaaz6606 (2020).

    Article  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  173. Khongorzul, P., Ling, C. J., Khan, F. U., Ihsan, A. U. & Zhang, J. Antibody–drug conjugates: a comprehensive review. Mol. Cancer Res. 18, 3–19 (2020).

    Article  CAS  PubMed  Google Scholar 

  174. Weiner, L. M., Murray, J. C. & Shuptrine, C. W. Antibody-based immunotherapy of cancer. Cell 148, 1081–1084 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Weiner, L. M., Surana, R. & Wang, S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat. Rev. Immunol. 10, 317–327 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Chia, C. S. B. A patent review on FDA‐approved antibody–drug conjugates, their linkers and drug payloads. ChemMedChem 17, e202200032 (2022).

    Article  CAS  PubMed  Google Scholar 

  177. Wang, F. et al. Supramolecular prodrug hydrogelator as an immune booster for checkpoint blocker-based immunotherapy. Sci. Adv. 6, eaaz8985 (2020).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  178. Wang, C. et al. In situ formed reactive oxygen species-responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy. Sci. Transl Med. 10, eaan3682 (2018).

    Article  PubMed  Google Scholar 

  179. Ye, Y. et al. A melanin-mediated cancer immunotherapy patch. Sci. Immunol. 2, eaan5692 (2017).

    Article  PubMed  Google Scholar 

  180. Yu, S. et al. Injectable bioresponsive gel depot for enhanced immune checkpoint blockade. Adv. Mater. 30, 1801527 (2018).

    Article  Google Scholar 

  181. Ruan, H. et al. A dual‐bioresponsive drug‐delivery depot for combination of epigenetic modulation and immune checkpoint blockade. Adv. Mater. 31, 1806957 (2019).

    Article  ADS  Google Scholar 

  182. Berraondo, P. et al. Cytokines in clinical cancer immunotherapy. Br. J. Cancer 120, 6–15 (2019).

    Article  CAS  PubMed  Google Scholar 

  183. Xue, D., Hsu, E., Fu, Y.-X. & Peng, H. Next-generation cytokines for cancer immunotherapy. Antib. Ther. 4, 123–133 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Chao, Y., Chen, Q. & Liu, Z. Smart injectable hydrogels for cancer immunotherapy. Adv. Funct. Mater. 30, 1902785 (2020).

    Article  CAS  Google Scholar 

  185. Erfani, A., Diaz, A. E. & Doyle, P. S. Hydrogel-enabled, local administration and combinatorial delivery of immunotherapies for cancer treatment. Mater. Today 65, 227–243 (2023).

    Article  CAS  Google Scholar 

  186. Falcone, N. et al. Peptide hydrogels as immunomaterials and their use in cancer immunotherapy delivery. Adv. Healthc. Mater. 16, e2301096 (2023).

    Article  Google Scholar 

  187. Zhang, J. et al. Immunostimulant hydrogel for the inhibition of malignant glioma relapse post-resection. Nat. Nanotechnol. 16, 538–548 (2021).

    Article  ADS  CAS  PubMed  Google Scholar 

  188. Jia, F. et al. Stabilizing RNA nanovaccines with transformable hyaluronan dynamic hydrogel for durable cancer immunotherapy. Adv. Funct. Mater. 33, 2204636 (2023).

    Article  CAS  Google Scholar 

  189. Grosskopf, A. K. et al. Delivery of CAR-T cells in a transient injectable stimulatory hydrogel niche improves treatment of solid tumors. Sci. Adv. 8, eabn8264 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Agarwalla, P. et al. Bioinstructive implantable scaffolds for rapid in vivo manufacture and release of CAR-T cells. Nat. Biotechnol. 40, 1250–1258 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Kennedy, L. B. & Salama, A. K. S. A review of cancer immunotherapy toxicity. CA Cancer J. Clin. 70, 86–104 (2020).

    Article  PubMed  Google Scholar 

  192. Postow, M. A., Sidlow, R. & Hellmann, M. D. Immune-related adverse events associated with immune checkpoint blockade. N. Engl. J. Med. 378, 158–168 (2018).

    Article  CAS  PubMed  Google Scholar 

  193. Kalbasi, A. & Ribas, A. Tumour-intrinsic resistance to immune checkpoint blockade. Nat. Rev. Immunol. 20, 25–39 (2020).

    Article  CAS  PubMed  Google Scholar 

  194. Flugel, C. L. et al. Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours. Nat. Rev. Clin. Oncol. 20, 49–62 (2023).

    Article  CAS  PubMed  Google Scholar 

  195. Gohil, S. H., Iorgulescu, J. B., Braun, D. A., Keskin, D. B. & Livak, K. J. Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy. Nat. Rev. Clin. Oncol. 18, 244–256 (2021).

    Article  PubMed  Google Scholar 

  196. Xu, J. et al. Near-infrared-triggered photodynamic therapy with multitasking upconversion nanoparticles in combination with checkpoint blockade for immunotherapy of colorectal cancer. ACS Nano 11, 4463–4474 (2017).

    Article  CAS  PubMed  Google Scholar 

  197. Ruan, S., Huang, Y., He, M. & Gao, H. Advanced biomaterials for cell‐specific modulation and restore of cancer immunotherapy. Adv. Sci. 9, 2200027 (2022).

    Article  CAS  Google Scholar 

  198. Pan, H., Zheng, M., Ma, A., Liu, L. & Cai, L. Cell/bacteria‐based bioactive materials for cancer immune modulation and precision therapy. Adv. Mater. 33, 2100241 (2021).

    Article  CAS  Google Scholar 

  199. Rodrigues, D. B., Reis, R. L. & Pirraco, R. P. How are natural-based polymers shaping the future of cancer immunotherapy — a review. Polym. Rev. https://doi.org/10.1080/15583724.2023.2234462 (2023).

  200. Wong, K. H., Lu, A., Chen, X. & Yang, Z. Natural ingredient-based polymeric nanoparticles for cancer treatment. Molecules 25, 3620 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  201. Munir, M. U. Nanomedicine penetration to tumor: challenges, and advanced strategies to tackle this issue. Cancers 14, 2904 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Zhang, Y. et al. Strategies to improve tumor penetration of nanomedicines through nanoparticle design. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 11, e1519 (2019).

    Article  PubMed  Google Scholar 

  203. Burugu, S., Dancsok, A. R. & Nielsen, T. O. Emerging targets in cancer immunotherapy. Semin. Cancer Biol. 52, 39–52 (2018).

    Article  CAS  PubMed  Google Scholar 

  204. Milling, L., Zhang, Y. & Irvine, D. J. Delivering safer immunotherapies for cancer. Adv. Drug Deliv. Rev. 114, 79–101 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Morris, E. C., Neelapu, S. S., Giavridis, T. & Sadelain, M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat. Rev. Immunol. 22, 85–96 (2022).

    Article  CAS  PubMed  Google Scholar 

  206. Gajewski, T. F. et al. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr. Opin. Immunol. 25, 268–276 (2013).

    Article  CAS  PubMed  Google Scholar 

  207. Boucher, Y., Baxter, L. T. & Jain, R. K. Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy. Cancer Res. 50, 4478–4484 (1990).

    CAS  PubMed  Google Scholar 

  208. Han, H. et al. Progress on the pathological tissue microenvironment barrier-modulated nanomedicine. Adv. Drug Deliv. Rev. 200, 115051 (2023).

    Article  CAS  PubMed  Google Scholar 

  209. Ribas, A. Clinical development of the anti-CTLA-4 antibody tremelimumab. Semin. Oncol. 37, 450–454 (2010).

    Article  MathSciNet  CAS  PubMed  Google Scholar 

  210. Linsley, P. S. & Nadler, S. G. The clinical utility of inhibiting CD28‐mediated costimulation. Immunol. Rev. 229, 307–321 (2009).

    Article  CAS  PubMed  Google Scholar 

  211. McKinlay, C. J. et al. Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals. Proc. Natl Acad. Sci. USA 114, E448–E456 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. June, C. H. et al. Engineered T cells for cancer therapy. Cancer Immunol. Immunother. 63, 969–975 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Zheng, P.-P., Kros, J. M. & Wang, G. Elusive neurotoxicity in T cell-boosting anticancer therapies. Trends Immunol. 40, 274–278 (2019).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

M.J.M. acknowledges support from the NIH Director’s New Innovator Award (DP2 TR002776), the American Cancer Society (no. RSG-22-122-01-ET) and an NSF CAREER Award (CBET-2145491). A.S.T. and R.M.H. acknowledge support from the National Science Foundation Graduate Research Fellowship (Award 1845298). D.M. acknowledges support from the Norman and Selma Kron Research Fellowship and the Robert Wood Johnson Foundation Health Policy Research Scholars.

Author information

Author notes

  1. These authors contributed equally: Lulu Xue, Ajay S. Thatte.

Authors and Affiliations

  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA

    Lulu Xue, Ajay S. Thatte, David Mai, Rebecca M. Haley, Ningqiang Gong, Xuexiang Han & Michael J. Mitchell

  2. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA

    David Mai, Neil C. Sheppard & Carl H. June

  3. Department of Bioengineering, Temple University, Philadelphia, PA, USA

    Karin Wang

  4. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Neil C. Sheppard & Carl H. June

  5. Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael J. Mitchell

  6. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael J. Mitchell

  7. Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael J. Mitchell

  8. Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael J. Mitchell

  9. Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michael J. Mitchell

Authors
  1. Lulu Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ajay S. Thatte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Mai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rebecca M. Haley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ningqiang Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xuexiang Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Neil C. Sheppard
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Carl H. June
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael J. Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

L.X., A.S.T. and M.J.M. conceived and outlined the general manuscript. L.X., A.S.T., D.M. and R.M.H. wrote the initial manuscript with contributions from X.H., N.G., K.W., N.C.S., C.H.J. and M.J.M. All authors edited the manuscript and figures and approved the final version for submission.

Corresponding author

Correspondence to Michael J. Mitchell.

Ethics declarations

Competing interests

N.C.S. holds equity in Tmunity Therapeutics. C.H.J. has received financial support from Novartis and has patents related to CAR therapy with royalties paid from Novartis to the University of Pennsylvania. C.H.J. is a scientific adviser for Alaunos, BluesphereBio, Cabaletta, Carisma, Cartography, Cellares, Cellcarta, Celldex, Danaher, Decheng, ImmuneSensor, Poseida, Verismo, Viracta and WIRB-Copernicus group and is a co-founder and holds equity in Capstan Therapeutics and Tmunity Therapeutics. The other authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Materials thanks Christopher Jewell, James Moon, who co-reviewed with Yujin Kim, and Omid Veiseh for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

Clinical trials: https://www.clinicaltrials.gov/

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xue, L., Thatte, A.S., Mai, D. et al. Responsive biomaterials: optimizing control of cancer immunotherapy. Nat Rev Mater 9, 100–118 (2024). https://doi.org/10.1038/s41578-023-00617-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41578-023-00617-2

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research