Skip to main content
SpringerLink
Log in

Nanotechnologies for enhancing cancer immunotherapy

  • Review Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Immunotherapy, a burgeoning field differs from traditional cancer treatments, is revolutionizing oncologic therapeutics. It aims to stimulate the innate and adaptive immune system of a patient to fight against tumor cells. However, low response rate and immune-related adverse effects (irAEs) remain problems during its management. A novel technology using nanomaterials may bring a solution. Various nanoparticles have been investigated as delivery systems to augment cancer therapeutic efficacy in the lab and clinic. In this review, we briefly summarize the connotation of immunotherapy, the application of nanotechnology in cancer, especially focusing on the synergistic effect of nanoplatform-based technology combined with cancer immunotherapy, hoping to make readers a deep insight into this interdisciplinary field.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Torre, L. A.; Bray, F.; Siegel, R. L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin.2015, 65, 87–108.

    Google Scholar 

  2. Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D. M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in globocan 2012. Int. J. Cancer2015, 136, E359–E386.

    CAS  Google Scholar 

  3. Fidler, M. M.; Bray, F.; Soerjomataram, I. The global cancer burden and human development: A review. Scand. J. Public Health2018, 46, 27–36.

    Google Scholar 

  4. Nam, J.; Son, S.; Park, K. S.; Zou, W. P.; Shea, L. D.; Moon, J. J. Cancer nanomedicine for combination cancer immunotherapy. Nat. Rev. Mater.2019, 4, 398–414.

    Google Scholar 

  5. Shi, J.; Kantoff, P. W.; Wooster, R.; Farokhzad, O. C. Cancer nanomedicine: Progress, challenges and opportunities. Nat. Rev. Cancer2017, 17, 20–37.

    CAS  Google Scholar 

  6. Kim, K. Y. Nanotechnology platforms and physiological challenges for cancer therapeutics. Nanomedicine: Nanotechnol., Biol. Med.2007, 3, 103–110.

    CAS  Google Scholar 

  7. Kalaydina, R. V.; Bajwa, K.; Qorri, B.; Decarlo, A.; Szewczuk, M. R. Recent advances in “smart” delivery systems for extended drug release in cancer therapy. int. J. Nanomedicine2018, 13, 4727–4745.

    CAS  Google Scholar 

  8. Van Der Meel, R.; Sulheim, E.; Shi, Y.; Kiessling, F.; Mulder, W. J. M.; Lammers, T. Smart cancer nanomedicine. Nat. Nanotechnol.2019, 14, 1007–1017.

    CAS  Google Scholar 

  9. Shao, K.; Singha, S.; Clemente-Casares, X.; Tsai, S.; Yang, Y.; Santamaria, P. Nanoparticle-based immunotherapy for cancer. ACS Nano2015, 9, 16–30.

    CAS  Google Scholar 

  10. Asadujjaman, M.; Cho, K. H.; Jang, D. J.; Kim, J. E.; Jee, J. P. Nanotechnology in the arena of cancer immunotherapy. Arch. Pharm. Res.2020, 43, 58–79.

    CAS  Google Scholar 

  11. Helmy, K. Y.; Patel, S. A.; Nahas, G. R.; Rameshwar, P. Cancer immunotherapy: Accomplishments to date and future promise. Ther. Deliv.2013, 4, 1307–1320.

    CAS  Google Scholar 

  12. Sun, Q. X.; Barz, M.; De Geest, B. G.; Diken, M.; Hennink, W. E.; Kiessling, F.; Lammers, T.; Shi, Y. Nanomedicine and macroscale materials in immuno-oncology. Chem. Soc. Rev.2019, 48, 351–381.

    CAS  Google Scholar 

  13. Shi, Y.; Lammers, T. Combining nanomedicine and immunotherapy. Acc. Chem. Res.2019, 52, 1543–1554.

    CAS  Google Scholar 

  14. Song, W. T.; Musetti, S. N.; Huang, L. Nanomaterials for cancer immunotherapy. Biomaterials2017, 148, 16–30.

    CAS  Google Scholar 

  15. Chen, D. S.; Mellman, I. Oncology meets immunology: The cancer-immunity cycle. Immunity2013, 39, 1–10.

    Google Scholar 

  16. Sanmamed, M. F.; Chen, L. P. A paradigm shift in cancer immunotherapy: From enhancement to normalization. Cell2018, 175, 313–326.

    CAS  Google Scholar 

  17. Dunn, G. P.; Bruce, A. T.; Ikeda, H.; Old, L. J.; Schreiber, R. D. Cancer immunoediting: From immunosurveillance to tumor escape. Nat. Immunol.2002, 3, 991–998.

    CAS  Google Scholar 

  18. Galluzzi, L.; Vacchelli, E.; Bravo-San Pedro, J. M.; Buqué, A.; Senovilla, L.; Baracco, E. E.; Bloy, N.; Castoldi, F.; Abastado, J. P.; Agostinis, P. et al. Classification of current anticancer immunotherapies. Oncotarget2014, 5, 12472–12508.

    Google Scholar 

  19. Demaria, O.; Cornen, S.; Daëron, M.; Morel, Y.; Medzhitov, R.; Vivier, E. Harnessing innate immunity in cancer therapy. Nature2019, 574, 45–56.

    CAS  Google Scholar 

  20. Abril-Rodriguez, G.; Ribas, A. SnapShot: Immune checkpoint inhibitors. Cancer Cell2017, 31, 848–848.e1.

    CAS  Google Scholar 

  21. Kennedy, L. B.; Salama, A. K. S. A review of cancer immunotherapy toxicity. CA Cancer J. Clin.2020, 70, 86–104.

    Google Scholar 

  22. Zhang, H. M.; Chen, J. B. Current status and future directions of cancer immunotherapy. J. Cancer2018, 9, 1773–1781.

    Google Scholar 

  23. Sakaguchi, S.; Mikami, N.; Wing, J. B.; Tanaka, A.; Ichiyama, K.; Ohkura, N. Regulatory T cells and human disease. Annu. Rev. Immunol.2020, 38, 541–566.

    CAS  Google Scholar 

  24. Vinay, D. S.; Ryan, E. P.; Pawelec, G.; Talib, W. H.; Stagg, J.; Elkord, E.; Lichtor, T.; Decker, W. K.; Whelan, R. L.; Kumara, H. M. C. S. et al. Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin. Cancer Biol.2015, 35, S185–S198.

    Google Scholar 

  25. Schreiber, R. D.; Old, L. J.; Smyth, M. J. Cancer immunoediting: Integrating immunity’s roles in cancer suppression and promotion. Science2011, 331, 1565–1570.

    CAS  Google Scholar 

  26. Motz, G. T.; Coukos, G. Deciphering and reversing tumor immune suppression. Immunity2013, 39, 61–73.

    CAS  Google Scholar 

  27. Jensen-Jarolim, E.; Bax, H. J.; Bianchini, R.; Crescioli, S.; Daniels-Wells, T. R.; Dombrowicz, D.; Fiebiger, E.; Gould, H. J.; Irshad, S.; Janda, J. et al. AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer. Allergy2018, 73, 328–340.

    CAS  Google Scholar 

  28. Makkouk, A.; Weiner, G. J. Cancer immunotherapy and breaking immune tolerance: New approaches to an old challenge. Cancer Res.2015, 75, 5–10.

    CAS  Google Scholar 

  29. Nishino, M.; Hatabu, H.; Hodi, F. S. Imaging of cancer immunotherapy: Current approaches and future directions. Radiology2019, 290, 9–22.

    Google Scholar 

  30. Mulder, W. J. M.; Ochando, J.; Joosten, L. A. B.; Fayad, Z. A.; Netea, M. G. Therapeutic targeting of trained immunity. Nat. Rev. Drug Discov.2019, 18, 553–566.

    CAS  Google Scholar 

  31. Fan, W. P.; Yung, B.; Huang, P.; Chen, X. Y. Nanotechnology for multimodal synergistic cancer therapy. Chem. Rev.2017, 117, 13566–13638.

    CAS  Google Scholar 

  32. Russell, L. M.; Liu, C. H.; Grodzinski, P. Nanomaterials innovation as an enabler for effective cancer interventions. Biomaterials2020, 242, 119926.

    CAS  Google Scholar 

  33. Liu, Y. Y.; Qiao, L. N.; Zhang, S. P.; Wan, G. Y.; Chen, B. W.; Zhou, P.; Zhang, N.; Wang, Y. S. Dual pH-responsive multifunctional nanoparticles for targeted treatment of breast cancer by combining immunotherapy and chemotherapy. Acta Biomater.2018, 66, 310–324.

    CAS  Google Scholar 

  34. Desale, S. S.; Raja, S. M.; Kim, J. O.; Mohapatra, B.; Soni, K. S.; Luan, H. T.; Williams, S. H.; Bielecki, T. A.; Feng, D.; Storck, M. et al. Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-aag show potent anti-tumor activity in erbb2-driven breast cancer models. J. Control. Release2015, 208, 59–66.

    CAS  Google Scholar 

  35. Wang, C.; Chen, S. Q.; Wang, Y. X.; Liu, X. R.; Hu, F. Q.; Sun, J. H.; Yuan, H. Lipase-triggered water-responsive “pandora’s box” for cancer therapy: Toward induced neighboring effect and enhanced drug penetration. Adv. Mater.2018, 30, 1706407.

    Google Scholar 

  36. Shi, L. L.; Hu, F.; Duan, Y. K.; Wu, W. B.; Dong, J. Q.; Meng, X. J.; Zhu, X. Y.; Liu, B. Hybrid nanospheres to overcome hypoxia and intrinsic oxidative resistance for enhanced photodynamic therapy. ACS Nano2020, 14, 2183–2190.

    CAS  Google Scholar 

  37. Gulzar, A.; Xu, J. T.; Yang, D.; Xu, L. G.; He, F.; Gai, S. L.; Yang, P. P. Nano-graphene oxide-ucnp-ce6 covalently constructed nanocomposites for nir-mediated bioimaging and ptt/pdt combinatorial therapy. Dalton Trans.2018, 47, 3931–3939.

    CAS  Google Scholar 

  38. Zhang, C.; Bu, W. B.; Ni, D. L.; Zhang, S. J.; Li, Q.; Yao, Z. W.; Zhang, J. W.; Yao, H. L.; Wang, Z.; Shi, J. L. Synthesis of iron nanometallic glasses and their application in cancer therapy by a localized fenton reaction. Angew. Chem., Int. Ed.2016, 55, 2101–2106.

    CAS  Google Scholar 

  39. Deepagan, V. G.; You, D. G.; Um, W.; Ko, H.; Kwon, S.; Choi, K. Y.; Yi, G. R.; Lee, J. Y.; Lee, D. S.; Kim, K. et al. Long-circulating au-TiO2 nanocomposite as a sonosensitizer for ros-mediated eradication of cancer. Nano Lett.2016, 16, 6257–6264.

    CAS  Google Scholar 

  40. Zhu, J. Y.; Zheng, D. W.; Zhang, M. K.; Yu, W. Y.; Qiu, W. X.; Hu, J. J.; Feng, J.; Zhang, X. Z. Preferential cancer cell self-recognition and tumor self-targeting by coating nanoparticles with homotypic cancer cell membranes. Nano Lett.2016, 16, 5895–5901.

    CAS  Google Scholar 

  41. Cun, X. L.; Ruan, S. B.; Chen, J. T.; Zhang, L.; Li, J. P.; He, Q.; Gao, H. L. A dual strategy to improve the penetration and treatment of breast cancer by combining shrinking nanoparticles with collagen depletion by losartan. Acta Biomater.2016, 31, 186–196.

    CAS  Google Scholar 

  42. Ma, T. C.; Liu, Y. D.; Wu, Q.; Luo, L. F.; Cui, Y. L.; Wang, X. H.; Chen, X. W.; Tan, L. F.; Meng, X. W. Quercetin-modified metal-organic frameworks for dual sensitization of radiotherapy in tumor tissues by inhibiting the carbonic anhydrase IX. ACS Nano2019, 13, 4209–4219.

    CAS  Google Scholar 

  43. Wang, J. T. W.; Klippstein, R.; Martincic, M.; Pach, E.; Feldman, R.; Seil, M.; Michel, Y.; Asker, D.; Sosabowski, J. K.; Kalbac, M. et al. Neutron activated 153Sm sealed in carbon nanocapsules for in vivo imaging and tumor radiotherapy. ACS Nano2020, 14, 129–141.

    CAS  Google Scholar 

  44. Tavallaie, R.; McCarroll, J.; Le Grand, M.; Ariotti, N.; Schuhmann, W.; Bakker, E.; Tilley, R. D.; Hibbert, D. B.; Kavallaris, M.; Gooding, J. J. Nucleic acid hybridization on an electrically reconfigurable network of gold-coated magnetic nanoparticles enables microrna detection in blood. Nat. Nanotechnol.2018, 13, 1066–1071.

    CAS  Google Scholar 

  45. Xie, Y.; Hang, Y.; Wang, Y. Z.; Sleightholm, R.; Prajapati, D. R.; Bader, J.; Yu, A.; Tang, W. M.; Jaramillo, L.; Li, J. et al. Stromal modulation and treatment of metastatic pancreatic cancer with local intraperitoneal triple mirna/sirna nanotherapy. ACS Nano2020, 14, 255–271.

    CAS  Google Scholar 

  46. Wang, S.; Liu, X.; Chen, S. Z.; Liu, Z. R.; Zhang, X. D.; Liang, X. J.; Li, L. L. Regulation of Ca2+ signaling for drug-resistant breast cancer therapy with mesoporous silica nanocapsule encapsulated doxorubicin/sirna cocktail. ACS Nano2019, 13, 274–283.

    CAS  Google Scholar 

  47. Yang, W. J.; Zhu, G. Z.; Wang, S.; Yu, G. C.; Yang, Z.; Lin, L. S.; Zhou, Z. J.; Liu, Y. J.; Dai, Y. L.; Zhang, F. W. et al. In situ dendritic cell vaccine for effective cancer immunotherapy. ACS Nano2019, 13, 3083–3094.

    CAS  Google Scholar 

  48. Qiu, F.; Becker, K. W.; Knight, F. C.; Baljon, J. J.; Sevimli, S.; Shae, D.; Gilchuk, P.; Joyce, S.; Wilson, J. T. Poly(propylacrylic acid)-peptide nanoplexes as a platform for enhancing the immunogenicity of neoantigen cancer vaccines. Biomaterials2018, 182, 82–91.

    CAS  Google Scholar 

  49. Gulla, S. K.; Rao, B. R.; Moku, G.; Jinka, S.; Nimmu, N. V.; Khalid, S.; Patra, C. R.; Chaudhuri, A. In vivo targeting of DNA vaccines to dendritic cells using functionalized gold nanoparticles. Biomater. Sci.2019, 7, 773–788.

    CAS  Google Scholar 

  50. Kranz, L. M.; Diken, M.; Haas, H.; Kreiter, S.; Loquai, C.; Reuter, K. C.; Meng, M.; Fritz, D.; Vascotto, F.; Hefesha, H. et al. Systemic rna delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature2016, 534, 396–401.

    Google Scholar 

  51. Colzani, B.; Pandolfi, L.; Hoti, A.; Iovene, P. A.; Natalello, A.; Avvakumova, S.; Colombo, M.; Prosperi, D. Investigation of antitumor activities of trastuzumab delivered by plga nanoparticles. Int. J. Nanomedicine2018, 13, 957–973.

    CAS  Google Scholar 

  52. Shae, D.; Becker, K. W.; Christov, P.; Yun, D. S.; Lytton-Jean, A. K. R.; Sevimli, S.; Ascano, M.; Kelley, M.; Johnson, D. B.; Balko, J. M. et al. Endosomolytic polymersomes increase the activity of cyclic dinucleotide sting agonists to enhance cancer immunotherapy. Nat. Nanotechnol.2019, 14, 269–278.

    CAS  Google Scholar 

  53. Steeland, S.; Vandenbroucke, R. E.; Libert, C. Nanobodies as therapeutics: Big opportunities for small antibodies. Drug Discov. Today2016, 21, 1076–1113.

    CAS  Google Scholar 

  54. Song, S. L.; Jin, X. X.; Zhang, L.; Zhao, C.; Ding, Y.; Ang, Q. Q.; Khaidav, O.; Shen, C. L. Pegylated and CD47-conjugated nano-ellipsoidal artificial antigen-presenting cells minimize phagocytosis and augment anti-tumor t-cell responses. Int. J. Nanomedicine2019, 14, 2465–2483.

    CAS  Google Scholar 

  55. Smith, T. T.; Stephan, S. B.; Moffett, H. F.; McKnight, L. E.; Ji, W. H.; Reiman, D.; Bonagofski, E.; Wohlfahrt, M. E.; Pillai, S. P. S.; Stephan, M. T. In situ programming of leukaemia-specific t cells using synthetic DNA nanocarriers. Nat. Nanotechnol.2017, 12, 813–820.

    CAS  Google Scholar 

  56. Lang, J. Y.; Zhao, X.; Qi, Y. Q.; Zhang, Y. L.; Han, X. X.; Ding, Y. P.; Guan, J. J.; Ji, T. J.; Zhao, Y.; Nie, G. J. Reshaping prostate tumor microenvironment to suppress metastasis via cancer-associated fibroblast inactivation with peptide-assembly-based nanosystem. ACS Nano2019, 13, 12357–12371.

    CAS  Google Scholar 

  57. Shen, S.; Li, H. J.; Chen, K. G.; Wang, Y. C.; Yang, X. Z.; Lian, Z. X.; Du, J. Z.; Wang, J. Spatial targeting of tumor-associated macrophages and tumor cells with a pH-sensitive cluster nanocarrier for cancer chemoimmunotherapy. Nano Lett.2017, 17, 3822–3829.

    CAS  Google Scholar 

  58. Liu, D. C.; Chen, B. L.; Mo, Y. L.; Wang, Z. H.; Qi, T.; Zhang, Q.; Wang, Y. G. Redox-activated porphyrin-based liposome remote-loaded with indoleamine 2,3-dioxygenase (IDO) inhibitor for synergistic photoimmunotherapy through induction of immunogenic cell death and blockage of ido pathway. Nano Lett.2019, 19, 6964–6976.

    CAS  Google Scholar 

  59. Lang, T. Q.; Liu, Y. R.; Zheng, Z.; Ran, W.; Zhai, Y. H.; Yin, Q.; Zhang, P. C.; Li, Y. P. Cocktail strategy based on spatio-temporally controlled nano device improves therapy of breast cancer. Adv. Mater.2019, 31, 1806202.

    Google Scholar 

  60. Gao, S. Q.; Li, T. Y.; Guo, Y.; Sun, C. X.; Xianyu, B. R.; Xu, H. P. Selenium-containing nanoparticles combine the NK cells mediated immunotherapy with radiotherapy and chemotherapy. Adv. Mater.2020, 32, 1907568.

    CAS  Google Scholar 

  61. Sun, Q. H.; Zhou, Z. X.; Qiu, N. S.; Shen, Y. Q. Rational design of cancer nanomedicine: Nanoproperty integration and synchronization. Adv. Mater.2017, 29, 1606628.

    Google Scholar 

  62. Goldberg, M. S. Improving cancer immunotherapy through nanotechnology. Nat. Rev. Cancer2019, 19, 587–602.

    CAS  Google Scholar 

  63. Zhou, Q.; Shao, S. Q.; Wang, J. Q.; Xu, C. H.; Xiang, J. J.; Piao, Y.; Zhou, Z. X.; Yu, Q. S.; Tang, J. B.; Liu, X. R. et al. Enzyme-activatable polymer-drug conjugate augments tumour penetration and treatment efficacy. Nat. Nanotechnol.2019, 14, 799–809.

    CAS  Google Scholar 

  64. Zhang, S. Q.; Liu, X.; Sun, Q. X.; Johnson, O.; Yang, T.; Chen, M. L.; Wang, J. H.; Chen, W. Cus@PDA-FA nanocomposites: A dual stimuli-responsive DOX delivery vehicle with ultrahigh loading level for synergistic photothermal-chemotherapies on breast cancer. J. Mater. Chem. B2020, 8, 1396–1404.

    CAS  Google Scholar 

  65. Zhu, X. H.; Tang, R.; Wang, S. G.; Chen, X. Y.; Hu, J. J.; Lei, C. Y.; Huang, Y.; Wang, H. H.; Nie, Z.; Yao, S. Z. Protein@inorganic nanodumpling system for high-loading protein delivery with activatable fluorescence and magnetic resonance bimodal imaging capabilities. ACS Nano2020, 14, 2172–2182.

    CAS  Google Scholar 

  66. Kosmides, A. K.; Sidhom, J. W.; Fraser, A.; Bessell, C. A.; Schneck, J. P. Dual targeting nanoparticle stimulates the immune system to inhibit tumor growth. ACS Nano2017, 11, 5417–5429.

    CAS  Google Scholar 

  67. Yong, T. Y.; Zhang, X. Q.; Bie, N. N.; Zhang, H. B.; Zhang, X. T.; Li, F. Y.; Hakeem, A.; Hu, J.; Gan, L.; Santos, H. A. et al. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy. Nat. Commun.2019, 10, 3838.

    Google Scholar 

  68. He, J. Y.; Li, C. C.; Ding, L.; Huang, Y. N.; Yin, X. L.; Zhang, J. F.; Zhang, J.; Yao, C. J.; Liang, M. M.; Pirraco, R. P. et al. Tumor targeting strategies of smart fluorescent nanoparticles and their applications in cancer diagnosis and treatment. Adv. Mater.2019, 31, 1902409.

    CAS  Google Scholar 

  69. Wang, X. H.; Wang, X. Y.; Jin, S. X.; Muhammad, N.; Guo, Z. J. Stimuli-responsive therapeutic metallodrugs. Chem. Rev.2019, 119, 1138–1192.

    CAS  Google Scholar 

  70. Xu, P. P.; Wang, X. Y.; Li, T. W.; Wu, H. H.; Li, L. L.; Chen, Z. L.; Zhang, L.; Guo, Z.; Chen, Q. W. Biomineralization-inspired nanozyme for single-wavelength laser activated photothermal-photodynamic synergistic treatment against hypoxic tumors. Nanoscale2020, 12, 4051–4060.

    CAS  Google Scholar 

  71. Dasgupta, S.; Rajapakshe, K.; Zhu, B. K.; Nikolai, B. C.; Yi, P.; Putluri, N.; Choi, J. M.; Jung, S. Y.; Coarfa, C.; Westbrook, T. F. et al. Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer. Nature2018, 556, 249–254.

    CAS  Google Scholar 

  72. Gao, R. F.; Li, D.; Xun, J.; Zhou, W.; Li, J.; Wang, J.; Liu, C.; Li, X. R.; Shen, W. Z.; Qiao, H. et al. CD44ICD promotes breast cancer stemness via PFKFB4-mediated glucose metabolism. Theranostics2018, 8, 6248–6262.

    CAS  Google Scholar 

  73. Sarkar Bhattacharya, S.; Thirusangu, P.; Jin, L.; Roy, D.; Jung, D.; Xiao, Y. N.; Staub, J.; Roy, B.; Molina, J. R.; Shridhar, V. PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and er stress as independent binary adaptive responses. Cell Death Dis.2019, 10, 725.

    Google Scholar 

  74. Mondal, S.; Roy, D.; Sarkar Bhattacharya, S.; Jin, L.; Jung, D.; Zhang, S.; Kalogera, E.; Staub, J.; Wang, Y. X.; Xuyang, W. et al. Therapeutic targeting of pfkfb3 with a novel glycolytic inhibitor pfk158 promotes lipophagy and chemosensitivity in gynecologic cancers. Int. J. Cancer2019, 144, 178–189.

    CAS  Google Scholar 

  75. Li, Y.; He, L. H.; Dong, H. Q.; Liu, Y. Q.; Wang, K.; Li, A.; Ren, T. B.; Shi, D. L.; Li, Y. Y. Fever-inspired immunotherapy based on photothermal cpg nanotherapeutics: The critical role of mild heat in regulating tumor microenvironment. Adv. Sci.2018, 5, 1700805.

    Google Scholar 

  76. Hu, X. C.; Lu, Y. L.; Shi, X. K.; Yao, T. M.; Dong, C. Y.; Shi, S. Integrating in situ formation of nanozymes with mesoporous polydopamine for combined chemo, photothermal and hypoxia-overcoming photodynamic therapy. Chem. Commun.2019, 55, 14785–14788.

    CAS  Google Scholar 

  77. Hu, X. C.; Lu, Y. L.; Dong, C. Y.; Zhao, W. R.; Wu, X. W.; Zhou, L. L.; Chen, L.; Yao, T. M.; Shi, S. A RuII polypyridyl alkyne complex based metal-organic frameworks for combined photodynamic/photothermal/chemotherapy. Chemistry2020, 26, 1668–1675.

    CAS  Google Scholar 

  78. Wang, W. Q.; Jin, Y. L.; Xu, Z. A.; Liu, X.; Bajwa, S. Z.; Khan, W. S.; Yu, H. J. Stimuli-activatable nanomedicines for chemodynamic therapy of cancer. Wiley Interdiscip. Rev. Nanomedicine. Nanobiotechnol.2020, 12, e1614.

    Google Scholar 

  79. Lin, L. S.; Song, J. B.; Song, L.; Ke, K. M.; Liu, Y. J.; Zhou, Z. J.; Shen, Z. Y.; Li, J.; Yang, Z.; Tang, W. et al. Simultaneous fenton-like ion delivery and glutathione depletion by Mno2-based nanoagent to enhance chemodynamic therapy. Angew. Chem., Int. Ed.2018, 57, 4902–4906.

    CAS  Google Scholar 

  80. Gao, F. L.; He, G. L.; Yin, H.; Chen, J.; Liu, Y. B.; Lan, C.; Zhang, S. R.; Yang, B. C. Titania-coated 2D gold nanoplates as nanoagents for synergistic photothermal/sonodynamic therapy in the second near-infrared window. Nanoscale2019, 11, 2374–2384.

    CAS  Google Scholar 

  81. Shen, Z. Y.; Song, J. B.; Zhou, Z. J.; Yung, B. C.; Aronova, M. A.; Li, Y.; Dai, Y. L.; Fan, W. P.; Liu, Y. J.; Li, Z. H. et al. Dotted core-shell nanoparticles for T1 -weighted MRI of tumors. Adv. Mater.2018, 30, 1803163.

    Google Scholar 

  82. Liu, Y. J.; Bhattarai, P.; Dai, Z. F.; Chen, X. Y. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem. Soc. Rev.2019, 48, 2053–2108.

    CAS  Google Scholar 

  83. Wong, X. Y.; Sena-Torralba, A.; Álvarez-Diduk, R.; Muthoosamy, K.; Merkoçi, A. Nanomaterials for nanotheranostics: Tuning their properties according to disease needs. ACS Nano2020, 14, 2585–2627.

    CAS  Google Scholar 

  84. Ali, E. S.; Sharker, S. M.; Islam, M. T.; Khan, I. N.; Shaw, S.; Rahman, M. A.; Uddin, S. J.; Shill, M. C.; Rehman, S.; Das, N. et al. Targeting cancer cells with nanotherapeutics and nanodiagnostics: Current status and future perspectives. Semin. Cancer Biol., in press, DOI: https://doi.org/10.1016/j.semcancer.2020.01.011.

  85. Wang, S.; Lin, J.; Wang, Z. T.; Zhou, Z. J.; Bai, R. L.; Lu, N.; Liu, Y. J.; Fu, X.; Jacobson, O.; Fan, W. P. et al. Core-satellite polydopamine-gadolinium-metallofullerene nanotheranostics for multimodal imaging guided combination cancer therapy. Adv. Mater.2017, 29, 1701013.

    Google Scholar 

  86. Lin, X.; Song, X. F.; Zhang, Y. W.; Cao, Y. B.; Xue, Y. N.; Wu, F. S.; Yu, F. Q.; Wu, M.; Zhu, X. J. Multifunctional theranostic nanosystems enabling photothermal-chemo combination therapy of triple-stimuli-responsive drug release with magnetic resonance imaging. Biomater. Sci.2020, 8, 1875–1884.

    CAS  Google Scholar 

  87. Yang, Z.; Song, J. B.; Tang, W.; Fan, W. P.; Dai, Y. L.; Shen, Z. Y.; Lin, L. S.; Cheng, S. Y.; Liu, Y. J.; Niu, G. et al. Stimuli-responsive nanotheranostics for real-time monitoring drug release by photoacoustic imaging. Theranostics2019, 9, 526–536.

    Google Scholar 

  88. Yang, Z.; Dai, Y. L.; Yin, C.; Fan, Q. L.; Zhang, W. S.; Song, J.; Yu, G. C.; Tang, W.; Fan, W. P.; Yung, B. C. et al. Activatable semiconducting theranostics: Simultaneous generation and ratiometric photoacoustic imaging of reactive oxygen species in vivo. Adv. Mater.2018, 30, 1707509.

    Google Scholar 

  89. Sung, Y. C.; Jin, P. R.; Chu, L. A.; Hsu, F. F.; Wang, M. R.; Chang, C. C.; Chiou, S. J.; Qiu, J. T.; Gao, D. Y.; Lin, C. C. et al. Delivery of nitric oxide with a nanocarrier promotes tumour vessel normalization and potentiates anti-cancer therapies. Nat. Nanotechnol.2019, 14, 1160–1169.

    CAS  Google Scholar 

  90. Truffi, M.; Mazzucchelli, S.; Bonizzi, A.; Sorrentino, L.; Allevi, R.; Vanna, R.; Morasso, C.; Corsi, F. Nano-strategies to target breast cancer-associated fibroblasts: Rearranging the tumor microenvironment to achieve antitumor efficacy. Int. J. Mol. Sci.2019, 20, 1263.

    CAS  Google Scholar 

  91. Chung, S. J.; Nagaraju, G. P.; Nagalingam, A.; Muniraj, N.; Kuppusamy, P.; Walker, A.; Woo, J.; Györffy, B.; Gabrielson, E.; Saxena, N. K. et al. ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis. Autophagy2017, 13, 1386–1403.

    CAS  Google Scholar 

  92. Katheder, N. S.; Khezri, R.; O’Farrell, F.; Schultz, S. W.; Jain, A.; Rahman, M. M.; Schink, K. O.; Theodossiou, T. A.; Johansen, T.; Juhász, G. et al. Microenvironmental autophagy promotes tumour growth. Nature2017, 541, 417–420.

    CAS  Google Scholar 

  93. Chen, Q.; Chen, J. W.; Yang, Z. J.; Xu, J.; Xu, L. G.; Liang, C.; Han, X.; Liu, Z. Nanoparticle-enhanced radiotherapy to trigger robust cancer immunotherapy. Adv. Mater.2019, 31, 1802228.

    Google Scholar 

  94. Gao, S.; Zhang, W. Z.; Wang, R. J.; Hopkins, S. P.; Spagnoli, J. C.; Racin, M.; Bai, L.; Li, L.; Jiang, W.; Yang, X. Y. et al. Nanoparticles encapsulating nitrosylated maytansine to enhance radiation therapy. ACS Nano2020, 14, 1468–1481.

    CAS  Google Scholar 

  95. Sarkar, S.; Levi-Polyachenko, N. Conjugated polymer nano-systems for hyperthermia, imaging and drug delivery. Adv. Drug Deliv. Rev., in press, DOI: https://doi.org/10.1016/j.addr.2020.01.002.

  96. Hotchkiss, R. D. The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. J. Biol. Chem.1948, 175, 315–332.

    CAS  Google Scholar 

  97. Kubik, T.; Bogunia-Kubik, K.; Sugisaka, M. Nanotechnology on duty in medical applications. Curr. Pharm. Biotechnol.2005, 6, 17–33.

    CAS  Google Scholar 

  98. Fire, A.; Xu, S. Q.; Montgomery, M. K.; Kostas, S. A.; Driver, S. E.; Mello, C. C. Potent and specific genetic interference by double-stranded rna in Caenorhabditis elegans. Nature1998, 391, 806–811.

    CAS  Google Scholar 

  99. Yatsunyk, L. A.; Mendoza, O.; Mergny, J. L. “Nano-oddities”: Unusual nucleic acid assemblies for DNA-based nanostructures and nanodevices. Acc. Chem. Res.2014, 47, 1836–1844.

    CAS  Google Scholar 

  100. Putnam, D. Polymers for gene delivery across length scales. Nat. Mater.2006, 5, 439–451.

    CAS  Google Scholar 

  101. Xin, Y.; Huang, M.; Guo, W. W.; Huang, Q.; Zhang, L. Z.; Jiang, G. Nano-based delivery of rnai in cancer therapy. Mol. Cancer2017, 16, 134.

    Google Scholar 

  102. Liu, Y. J.; Zou, Y.; Feng, C.; Lee, A.; Yin, J. L.; Chung, R.; Park, J. B.; Rizos, H.; Tao, W.; Zheng, M. et al. Charge conversional biomimetic nanocomplexes as a multifunctional platform for boosting orthotopic glioblastoma rnai therapy. Nano Lett.2020, 20, 1637–1646.

    CAS  Google Scholar 

  103. Yu, T.; Guo, F. F.; Yu, Y. N.; Sun, T. T.; Ma, D.; Han, J. X.; Qian, Y.; Kryczek, I.; Sun, D. F.; Nagarsheth, N. et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell2017, 170, 548–563.e16.

    CAS  Google Scholar 

  104. Eedunuri, V. K.; Rajapakshe, K.; Fiskus, W.; Geng, C. D.; Chew, S. A.; Foley, C.; Shah, S. S.; Shou, J.; Mohamed, J. S.; Coarfa, C. et al. miR-137 targets p160 steroid receptor coactivators SRC1, SRC2, and SRC3 and inhibits cell proliferation. Mol. Endocrinol.2015, 29, 1170–1183.

    CAS  Google Scholar 

  105. Vodnala, S. K.; Eil, R.; Kishton, R. J.; Sukumar, M.; Yamamoto, T. N.; Ha, N. H.; Lee, P. H.; Shin, M.; Patel, S. J.; Yu, Z. Y. et al. T cell stemness and dysfunction in tumors are triggered by a common mechanism. Science2019, 363, eaau0135.

    CAS  Google Scholar 

  106. Loginov, V. I.; Burdennyy, A. M.; Pronina, I. V.; Khokonova, V. V.; Kurevljov, S. V.; Kazubskaya, T. P.; Kushlinskii, N. E.; Braga, E. A. Novel miRNA genes hypermethylated in breast cancer. Mol. Biol.2016, 50, 705–709.

    CAS  Google Scholar 

  107. Zhang, D.; Tang, Z. Y.; Huang, H.; Zhou, G. L.; Cui, C.; Weng, Y. J.; Liu, W. C.; Kim, S.; Lee, S.; Perez-Neut, M. et al. Metabolic regulation of gene expression by histone lactylation. Nature2019, 574, 575–580.

    CAS  Google Scholar 

  108. Hoos, A. Development of immuno-oncology drugs—from CTLA4 to PD1 to the next generations. Nat. Rev. Drug Discov.2016, 15, 235–247.

    CAS  Google Scholar 

  109. Dong, H.; Xu, X.; Wang, L. K.; Mo, R. Advances in living cell-based anticancer therapeutics. Biomater. Sci.2020, 8, 2344–2365.

    CAS  Google Scholar 

  110. Xu, X.; Li, T.; Shen, S. Y.; Wang, J. Q.; Abdou, P.; Gu, Z.; Mo, R. Advances in engineering cells for cancer immunotherapy. Theranostics2019, 9, 7889–7905.

    CAS  Google Scholar 

  111. Abdou, P.; Wang, Z. J.; Chen, Q.; Chan, A.; Zhou, D. R.; Gunadhi, V.; Gu, Z. Advances in engineering local drug delivery systems for cancer immunotherapy. Wiley Interdiscip. Rev. Nanomedicine. Nanobiotechnol., in press, DOI: https://doi.org/10.1002/wnan.1632.

  112. Sharma, P.; Allison, J. P. The future of immune checkpoint therapy. Science2015, 348, 56–61.

    CAS  Google Scholar 

  113. Sharma, P.; Allison, J. P. Immune checkpoint targeting in cancer therapy: Toward combination strategies with curative potential. Cell2015, 161, 205–214.

    CAS  Google Scholar 

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

    Google Scholar 

  115. Wei, X. X.; Fong, L.; Small, E. J. Prostate cancer immunotherapy with sipuleucel-T: Current standards and future directions. Expert Rev. Vaccines2015, 14, 1529–1541.

    CAS  Google Scholar 

  116. Van Der Bruggen, P.; Traversari, C.; Chomez, P.; Lurquin, C.; De Plaen, E.; Van den Eynde, B.; Knuth, A.; Boon, T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science1991, 254, 1643–1647.

    CAS  Google Scholar 

  117. Song, Q.; Zhang, C. D.; Wu, X. H. Therapeutic cancer vaccines: From initial findings to prospects. Immunol. Lett.2018, 196, 11–21.

    CAS  Google Scholar 

  118. Zhang, Y.; Lin, S. B.; Wang, X. Y.; Zhu, G. Z. Nanovaccines for cancer immunotherapy. Wiley Interdiscip. Rev. Nanomedicine. Nanobiotechnol.2019, 11, e1559.

    Google Scholar 

  119. Palucka, K.; Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer2012, 12, 265–277.

    CAS  Google Scholar 

  120. Zhang, J. X.; Mai, J. H.; Li, F.; Shen, J. L.; Zhang, G. D.; Li, J.; Hinkle, L. E.; Lin, D.; Liu, X. W.; Li, Z. et al. Investigation of parameters that determine nano-DC vaccine transport. Biomed. Microdevices2019, 21, 39.

    Google Scholar 

  121. Xia, X. J.; Mai, J. H.; Xu, R.; Perez, J. E. T.; Guevara, M. L.; Shen, Q.; Mu, C. F.; Tung, H. Y.; Corry, D. B.; Evans, S. E. et al. Porous silicon microparticle potentiates anti-tumor immunity by enhancing cross-presentation and inducing type I interferon response. Cell Rep.2015, 11, 957–966.

    CAS  Google Scholar 

  122. Duong, H. T. T.; Thambi, T.; Yin, Y.; Kim, S. H.; Nguyen, T. L.; Phan, V. H. G.; Kim, J.; Jeong, J. H.; Lee, D. S. Degradation-regulated architecture of injectable smart hydrogels enhances humoral immune response and potentiates antitumor activity in human lung carcinoma. Biomaterials2020, 230, 119599.

    CAS  Google Scholar 

  123. Milani, A.; Sangiolo, D.; Montemurro, F.; Aglietta, M.; Valabrega, G. Active immunotherapy in HER2 overexpressing breast cancer: Current status and future perspectives. Ann. Oncol.2013, 24, 1740–1748.

    CAS  Google Scholar 

  124. Yang, Z. G.; Ma, Y. F.; Zhao, H.; Yuan, Y.; Kim, B. Y. S. Nanotechnology platforms for cancer immunotherapy. Wiley Interdiscip. Rev. Nanomedicine. Nanobiotechnol.2020, 12, e1590.

    Google Scholar 

  125. Li, A. W.; Sobral, M. C.; Badrinath, S.; Choi, Y.; Graveline, A.; Stafford, A. G.; Weaver, J. C.; Dellacherie, M. O.; Shih, T. Y.; Ali, O. A. et al. A facile approach to enhance antigen response for personalized cancer vaccination. Nat. Mater.2018, 17, 528–534.

    CAS  Google Scholar 

  126. Wilson, J. T.; Postma, A.; Keller, S.; Convertine, A. J.; Moad, G.; Rizzardo, E.; Meagher, L.; Chiefari, J.; Stayton, P. S. Enhancement of MHC-I antigen presentation via architectural control of pH-responsive, endosomolytic polymer nanoparticles. AAPS J.2015, 17, 358–369.

    CAS  Google Scholar 

  127. Alspach, E.; Lussier, D. M.; Miceli, A. P.; Kizhvatov, I.; DuPage, M.; Luoma, A. M.; Meng, W.; Lichti, C. F.; Esaulova, E.; Vomund, A. N. et al. MHC-II neoantigens shape tumour immunity and response to immunotherapy. Nature2019, 574, 696–701.

    CAS  Google Scholar 

  128. Liu, M. A. DNA vaccines: An historical perspective and view to the future. Immunol. Rev.2011, 239, 62–84.

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  130. Lu, Y. X.; Wu, F. P.; Duan, W. H.; Mu, X.; Fang, S.; Lu, N. N.; Zhou, X. F.; Kong, W. Engineering a “PEG-g-PEI/DNA nanoparticle-in-PLGA microsphere” hybrid controlled release system to enhance immunogenicity of DNA vaccine. Mater. Sci. Eng. C2020, 106, 110294.

    Google Scholar 

  131. Lee, K.; Kim, M.; Seo, Y.; Lee, H. Development of mRNA vaccines and their prophylactic and therapeutic applications. Nano Res.2018, 11, 5173–5192.

    CAS  Google Scholar 

  132. Li, J. C.; Zhen, X.; Lyu, Y.; Jiang, Y. Y.; Huang, J. G.; Pu, K. Y. Cell membrane coated semiconducting polymer nanoparticles for enhanced multimodal cancer phototheranostics. ACS Nano2018, 12, 8520–8530.

    CAS  Google Scholar 

  133. Guo, Y. Y.; Wang, D.; Song, Q. L.; Wu, T. T.; Zhuang, X. T.; Bao, Y. L.; Kong, M.; Qi, Y.; Tan, S. W.; Zhang, Z. P. Erythrocyte membrane-enveloped polymeric nanoparticles as nanovaccine for induction of antitumor immunity against melanoma. ACS Nano2015, 9, 6918–6933.

    CAS  Google Scholar 

  134. Zhou, J. R.; Kroll, A. V.; Holay, M.; Fang, R. H.; Zhang, L. F. Biomimetic nanotechnology toward personalized vaccines. Adv. Mater.2020, 32, 1901255.

    CAS  Google Scholar 

  135. Hu, Q. Y.; Sun, W. J.; Qian, C. E.; Wang, C.; Bomba, H. N.; Gu, Z. Anticancer platelet-mimicking nanovehicles. Adv. Mater.2015, 27, 7043–7050.

    CAS  Google Scholar 

  136. Liu, R.; An, Y.; Jia, W. F.; Wang, Y. S.; Wu, Y.; Zhen, Y. H.; Cao, J.; Gao, H. L. Macrophage-mimic shape changeable nanomedicine retained in tumor for multimodal therapy of breast cancer. J. Control. Release2020, 321, 589–601.

    CAS  Google Scholar 

  137. Gao, C. Y.; Lin, Z. H.; Wu, Z. G.; Lin, X. K.; He, Q. Stem-cell-membrane camouflaging on near-infrared photoactivated upconversion nanoarchitectures for in vivo remote-controlled photodynamic therapy. ACS Appl. Mater. Interfaces2016, 8, 34252–34260.

    CAS  Google Scholar 

  138. Zou, S. J.; Wang, B. L.; Wang, C.; Wang, Q. Q.; Zhang, L. M. Cell membrane-coated nanoparticles: Research advances. Nanomedicine2020, 15, 625–641.

    CAS  Google Scholar 

  139. Chen, M. S.; Ouyang, H. C.; Zhou, S. Y.; Li, J. Y.; Ye, Y. B. PLGA-nanoparticle mediated delivery of anti-OX40 monoclonal antibody enhances anti-tumor cytotoxic t cell responses. Cell. Immunol.2014, 287, 91–99.

    CAS  Google Scholar 

  140. Chen, Q.; Wang, C.; Zhang, X. D.; Chen, G. J.; Hu, Q. Y.; Li, H. J.; Wang, J. Q.; Wen, D.; Zhang, Y. Q.; Lu, Y. F. et al. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat. Nanotechnol.2019, 14, 89–97.

    CAS  Google Scholar 

  141. Ma, L. L.; Zhu, M.; Gai, J. W.; Li, G. H.; Chang, Q.; Qiao, P.; Cao, L. L.; Chen, W. Q.; Zhang, S. Y.; Wan, Y. K. Preclinical development of a novel CD47 nanobody with less toxicity and enhanced anti-cancer therapeutic potential. J. Nanobiotechnol.2020, 18, 12.

    CAS  Google Scholar 

  142. De Bruijn, H. S.; Mashayekhi, V.; Schreurs, T. J. L.; Van Driel, P. B. A. A.; Strijkers, G. J.; Van Diest, P. J.; Lowik, C. W. G. M.; Seynhaeve, A. L. B.; Ten Hagen, T. L. M.; Prompers, J. J. et al. Acute cellular and vascular responses to photodynamic therapy using egfr-targeted nanobody-photosensitizer conjugates studied with intravital optical imaging and magnetic resonance imaging. Theranostics2020, 10, 2436–2452.

    Google Scholar 

  143. Hassani, M.; Hajari Taheri, F.; Sharifzadeh, Z.; Arashkia, A.; Hadjati, J.; Van Weerden, W. M.; Abdoli, S.; Modarressi, M. H.; Abolhassani, M. Engineered jurkat cells for targeting prostate-specific membrane antigen on prostate cancer cells by nanobody-based chimeric antigen receptor. Iran. Biomed. J.2020, 24, 81–88.

    Google Scholar 

  144. Huang, Y. H.; Zhu, C.; Kondo, Y.; Anderson, A. C.; Gandhi, A.; Russell, A.; Dougan, S. K.; Petersen, B. S.; Melum, E.; Pertel, T. et al. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature2015, 517, 386–390.

    CAS  Google Scholar 

  145. ElTanbouly, M. A.; Zhao, Y. D.; Nowak, E.; Li, J. N.; Schaafsma, E.; Le Mercier, I.; Ceeraz, S.; Lines, J. L.; Peng, C. W.; Carriere, C. et al. VISTA is a checkpoint regulator for naive T cell quiescence and peripheral tolerance. Science2020, 367, eaay0524.

    CAS  Google Scholar 

  146. Jafari, S.; Molavi, O.; Kahroba, H.; Hejazi, M. S.; Maleki-Dizaji, N.; Barghi, S.; Kiaie, S. H.; Jadidi-Niaragh, F. Clinical application of immune checkpoints in targeted immunotherapy of prostate cancer. Cell. Mol. Life Sci., in press, DOI: https://doi.org/10.1007/s00018-020-03459-1.

  147. Greenwald, R. J.; Freeman, G. J.; Sharpe, A. H. The B7 family revisited. Annu. Rev. Immunol.2005, 23, 515–548.

    Google Scholar 

  148. Wei, S. C.; Levine, J. H.; Cogdill, A. P.; Zhao, Y.; Anang, N. A. S.; Andrews, M. C.; Sharma, P.; Wang, J.; Wargo, J. A.; Pe’er, D. et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell2017, 170, 1120–1133.e17.

    CAS  Google Scholar 

  149. Ordikhani, F.; Uehara, M.; Kasinath, V.; Dai, L.; Eskandari, S. K.; Bahmani, B.; Yonar, M.; Azzi, J. R.; Haik, Y.; Sage, P. T. et al. Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity. JCI Insight2018, 3, 122700.

    Google Scholar 

  150. Hu, Q. Y.; Sun, W. J.; Wang, J. Q.; Ruan, H. T.; Zhang, X. D.; Ye, Y. Q.; Shen, S.; Wang, C.; Lu, W. Y.; Cheng, K. et al. Conjugation of haematopoietic stem cells and platelets decorated with anti-pd-1 antibodies augments anti-leukaemia efficacy. Nat. Biomed. Eng.2018, 2, 831–840.

    CAS  Google Scholar 

  151. Zhu, Y. Y.; An, X.; Zhang, X.; Qiao, Y.; Zheng, T. S.; Li, X. B. STING: A master regulator in the cancer-immunity cycle. Mol. Cancer2019, 18, 152.

    Google Scholar 

  152. Luo, M.; Wang, H.; Wang, Z. H.; Cai, H. C.; Lu, Z. G.; Li, Y.; Du, M. J.; Huang, G.; Wang, C. S.; Chen, X. et al. A STING-activating nanovaccine for cancer immunotherapy. Nat. Nanotechnol.2017, 12, 648–654.

    CAS  Google Scholar 

  153. Ruan, H. T.; Hu, Q. Y.; Wen, D.; Chen, Q.; Chen, G. J.; Lu, Y. F.; Wang, J. Q.; Cheng, H.; Lu, W. Y.; Gu, Z. A dual-bioresponsive drug-delivery depot for combination of epigenetic modulation and immune checkpoint blockade. Adv. Mater.2019, 31, 1806957.

    Google Scholar 

  154. Chen, Q.; Wang, C.; Chen, G. J.; Hu, Q. Y.; Gu, Z. Delivery strategies for immune checkpoint blockade. Adv. Healthc. Mater.2018, 7, 1800424.

    Google Scholar 

  155. Schmid, P.; Adams, S.; Rugo, H. S.; Schneeweiss, A.; Barrios, C. H.; Iwata, H.; Dieras, V.; Hegg, R.; Im, S. A.; Shaw Wright, G. et al. Atezolizumab and Nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med.2018, 379, 2108–2121.

    CAS  Google Scholar 

  156. Larkin, J.; Chiarion-Sileni, V.; Gonzalez, R.; Grob, J. J.; Cowey, C. L.; Lao, C. D.; Schadendorf, D.; Dummer, R.; Smylie, M.; Rutkowski, P. et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med.2015, 373, 23–34.

    Google Scholar 

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

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  159. June, C. H.; Sadelain, M. Chimeric antigen receptor therapy. N. Engl. J. Med.2018, 379, 64–73.

    CAS  Google Scholar 

  160. Brown, C. E.; Mackall, C. L. CAR T cell therapy: Inroads to response and resistance. Nat. Rev. Immunol.2019, 19, 73–74.

    CAS  Google Scholar 

  161. Tang, J.; Hubbard-Lucey, V. M.; Pearce, L.; O’Donnell-Tormey, J.; Shalabi, A. The global landscape of cancer cell therapy. Nat. Rev. Drug Discov.2018, 17, 465–466.

    CAS  Google Scholar 

  162. June, C. H.; O’Connor, R. S.; Kawalekar, O. U.; Ghassemi, S.; Milone, M. C. CAR T cell immunotherapy for human cancer. Science2018, 359, 1361–1365.

    CAS  Google Scholar 

  163. Hinrichs, C. S.; Rosenberg, S. A. Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol. Rev.2014, 257, 56–71.

    CAS  Google Scholar 

  164. Zhao, L. J.; Cao, Y. J. Engineered T cell therapy for cancer in the clinic. Front. Immunol.2019, 10, 2250.

    CAS  Google Scholar 

  165. Cheung, A. S.; Zhang, D. K. Y.; Koshy, S. T.; Mooney, D. J. Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells. Nat. Biotechnol.2018, 36, 160–169.

    CAS  Google Scholar 

  166. Rhodes, K. R.; Green, J. J. Nanoscale artificial antigen presenting cells for cancer immunotherapy. Mol. Immunol.2018, 98, 13–18.

    CAS  Google Scholar 

  167. Meyer, R. A.; Sunshine, J. C.; Perica, K.; Kosmides, A. K.; Aje, K.; Schneck, J. P.; Green, J. J. Biodegradable nanoellipsoidal artificial antigen presenting cells for antigen specific T-cell activation. Small2015, 11, 1519–1525.

    CAS  Google Scholar 

  168. Olden, B. R.; Perez, C. R.; Wilson, A. L.; Cardle, I. I.; Lin, Y. S.; Kaehr, B.; Gustafson, J. A.; Jensen, M. C.; Pun, S. H. Cell-templated silica microparticles with supported lipid bilayers as artificial antigen-presenting cells for T cell activation. Adv. Healthc. Mater.2019, 8, 1801188.

    Google Scholar 

  169. Stephan, M. T.; Moon, J. J.; Um, S. H.; Bershteyn, A.; Irvine, D. J. Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat. Med.2010, 16, 1035–1041.

    CAS  Google Scholar 

  170. Stephan, M. T.; Stephan, S. B.; Bak, P.; Chen, J. Z.; Irvine, D. J. Synapse-directed delivery of immunomodulators using T-cell-conjugated nanoparticles. Biomaterials2012, 33, 5776–5787.

    CAS  Google Scholar 

  171. Huang, B.; Abraham, W. D.; Zheng, Y. R.; Bustamante López, S. C.; Luo, S. S.; Irvine, D. J. Active targeting of chemotherapy to disseminated tumors using nanoparticle-carrying T cells. Sci. Transl. Med.2015, 7, 291ra94.

    Google Scholar 

  172. Ma, L. Y.; Dichwalkar, T.; Chang, J. Y. H.; Cossette, B.; Garafola, D.; Zhang, A. Q.; Fichter, M.; Wang, C. S.; Liang, S.; Silva, M. et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science2019, 365, 162–168.

    CAS  Google Scholar 

  173. Chen, Q.; Hu, Q. Y.; Dukhovlinova, E.; Chen, G. J.; Ahn, S.; Wang, C.; Ogunnaike, E. A.; Ligler, F. S.; Dotti, G.; Gu, Z. Photothermal therapy promotes tumor infiltration and antitumor activity of CAR T cells. Adv. Mater.2019, 31, 1900192.

    Google Scholar 

  174. Beatty, G. L.; O’Hara, M. H.; Lacey, S. F.; Torigian, D. A.; Nazimuddin, F.; Chen, F.; Kulikovskaya, I. M.; Soulen, M. C.; McGarvey, M.; Nelson, A. M. et al. Activity of mesothelin-specific chimeric antigen receptor t cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology2018, 155, 29–32.

    CAS  Google Scholar 

  175. Lim, W. A.; June, C. H. The principles of engineering immune cells to treat cancer. Cell2017, 168, 724–740.

    CAS  Google Scholar 

  176. Millar, D. G.; Ramjiawan, R. R.; Kawaguchi, K.; Gupta, N.; Chen, J.; Zhang, S. F.; Nojiri, T.; Ho, W. W.; Aoki, S.; Jung, K. et al. Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy. Nat. Biotechnol.2020, 38, 420–425.

    CAS  Google Scholar 

  177. Thakkar, S.; Sharma, D.; Kalia, K.; Tekade, R. K. Tumor microenvironment targeted nanotherapeutics for cancer therapy and diagnosis: A review. Acta Biomater.2020, 101, 43–68.

    CAS  Google Scholar 

  178. Chen, Q.; Liu, G. X.; Liu, S.; Su, H. Y.; Wang, Y.; Li, J. Y.; Luo, C. Remodeling the tumor microenvironment with emerging nano-therapeutics. Trends Pharmacol. Sci.2018, 39, 59–74.

    Google Scholar 

  179. Sahai, E.; Astsaturov, I.; Cukierman, E.; DeNardo, D. G.; Egeblad, M.; Evans, R. M.; Fearon, D.; Greten, F. R.; Hingorani, S. R.; Hunter, T. et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer2020, 20, 174–186.

    CAS  Google Scholar 

  180. Fukumura, D.; Xavier, R.; Sugiura, T.; Chen, Y.; Park, E. C.; Lu, N. F.; Selig, M.; Nielsen, G.; Taksir, T.; Jain, R. K. et al. Tumor induction of VEGF promoter activity in stromal cells. Cell1998, 94, 715–725.

    CAS  Google Scholar 

  181. Bhome, R.; Goh, R. W.; Bullock, M. D.; Pillar, N.; Thirdborough, S. M.; Mellone, M.; Mirnezami, R.; Galea, D.; Veselkov, K.; Gu, Q. et al. Exosomal microRNAs derived from colorectal cancer-associated fibroblasts: Role in driving cancer progression. Aging2017, 9, 2666–2694.

    CAS  Google Scholar 

  182. Kojima, Y.; Acar, A.; Eaton, E. N.; Mellody, K. T.; Scheel, C.; Ben-Porath, I.; Onder, T. T.; Wang, Z. C.; Richardson, A. L.; Weinberg, R. A. et al. Autocrine TGF-β and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc. Natl. Acad. Sci. USA2010, 107, 20009–20014.

    CAS  Google Scholar 

  183. Hou, L.; Liu, Q.; Shen, L. M.; Liu, Y.; Zhang, X. Q.; Chen, F. Q.; Huang, L. Nano-delivery of fraxinellone remodels tumor microenvironment and facilitates therapeutic vaccination in desmoplastic melanoma. Theranostics2018, 8, 3781–3796.

    CAS  Google Scholar 

  184. Hu, C. H.; Liu, X. Y.; Ran, W.; Meng, J.; Zhai, Y. H.; Zhang, P. C.; Yin, Q.; Yu, H. J.; Zhang, Z. W.; Li, Y. P. Regulating cancer associated fibroblasts with losartan-loaded injectable peptide hydrogel to potentiate chemotherapy in inhibiting growth and lung metastasis of triple negative breast cancer. Biomaterials2017, 144, 60–72.

    CAS  Google Scholar 

  185. Zhang, B.; Jin, K.; Jiang, T.; Wang, L. T.; Shen, S.; Luo, Z. M.; Tuo, Y. Y.; Liu, X. P.; Hu, Y.; Pang, Z. Q. Celecoxib normalizes the tumor microenvironment and enhances small nanotherapeutics delivery to A549 tumors in nude mice. Sci. Rep.2017, 7, 10071.

    Google Scholar 

  186. Li, W.; Zhao, X. X.; Du, B.; Li, X.; Liu, S. H.; Yang, X. Y.; Ding, H.; Yang, W. D.; Pan, F.; Wu, X. B. et al. Gold nanoparticle-mediated targeted delivery of recombinant human endostatin normalizes tumour vasculature and improves cancer therapy. Sci. Rep.2016, 6, 30619.

    CAS  Google Scholar 

  187. Lewis, C. E.; Pollard, J. W. Distinct role of macrophages in different tumor microenvironments. Cancer Res.2006, 66, 605–612.

    CAS  Google Scholar 

  188. Ngambenjawong, C.; Gustafson, H. H.; Pun, S. H. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv. Drug Deliv. Rev.2017, 114, 206–221.

    CAS  Google Scholar 

  189. Okabe, Y.; Medzhitov, R. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell2014, 157, 832–844.

    CAS  Google Scholar 

  190. Gordon, S.; Martinez, F. O. Alternative activation of macrophages: Mechanism and functions. Immunity2010, 32, 593–604.

    CAS  Google Scholar 

  191. Rodell, C. B.; Arlauckas, S. P.; Cuccarese, M. F.; Garris, C. S.; Li, R.; Ahmed, M. S.; Kohler, R. H.; Pittet, M. J.; Weissleder, R. TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy. Nat. Biomed. Eng.2018, 2, 578–588.

    CAS  Google Scholar 

  192. Chen, L.; Zhou, L. L.; Wang, C. H.; Han, Y.; Lu, Y. L.; Liu, J.; Hu, X. C.; Yao, T. M.; Lin, Y.; Liang, S. J. et al. Tumor-targeted drug and CpG delivery system for phototherapy and docetaxel-enhanced immunotherapy with polarization toward M1-type macrophages on triple negative breast cancers. Adv. Mater.2019, 31, 1904997.

    CAS  Google Scholar 

  193. Tsai, S. J.; Andorko, J. I.; Zeng, X. B.; Gammon, J. M.; Jewell, C. M. Polyplex interaction strength as a driver of potency during cancer immunotherapy. Nano Res.2018, 11, 5642–5656.

    CAS  Google Scholar 

  194. Kim, S. Y.; Kim, S.; Kim, J. E.; Lee, S. N.; Shin, I. W.; Shin, H. S.; Jin, S. M.; Noh, Y. W.; Kang, Y. J.; Kim, Y. S. et al. Lyophilizable and multifaceted toll-like receptor 7/8 agonist-loaded nanoemulsion for the reprogramming of tumor microenvironments and enhanced cancer immunotherapy. ACS Nano2019, 13, 12671–12686.

    CAS  Google Scholar 

  195. Cheng, N.; Watkins-Schulz, R.; Junkins, R. D.; David, C. N.; Johnson, B. M.; Montgomery, S. A.; Peine, K. J.; Darr, D. B.; Yuan, H.; McKinnon, K. P. et al. A nanoparticle-incorporated STING activator enhances antitumor immunity in PD-L1-insensitive models of triple-negative breast cancer. JCI Insight2018, 3, e120638.

    Google Scholar 

  196. Conde, J.; Bao, C. C.; Tan, Y. Q.; Cui, D. X.; Edelman, E. R.; Azevedo, H. S.; Byrne, H. J.; Artzi, N.; Tian, F. R. Dual targeted immunotherapy via in vivo delivery of biohybrid RNAi-peptide nanoparticles to tumor-associated macrophages and cancer cells. Adv. Funct. Mater.2015, 25, 4183–4194.

    CAS  Google Scholar 

  197. Ma, S.; Song, W. T.; Xu, Y. D.; Si, X. H.; Zhang, D. W.; Lv, S. X.; Yang, C. G.; Ma, L. L.; Tang, Z. H.; Chen, X. S. Neutralizing tumor-promoting inflammation with polypeptide-dexamethasone conjugate for microenvironment modulation and colorectal cancer therapy. Biomaterials2020, 232, 119676.

    CAS  Google Scholar 

  198. Colegio, O. R.; Chu, N. Q.; Szabo, A. L.; Chu, T.; Rhebergen, A. M.; Jairam, V.; Cyrus, N.; Brokowski, C. E.; Eisenbarth, S. C.; Phillips, G. M. et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature2014, 513, 559–563.

    CAS  Google Scholar 

  199. Saeed, M.; Gao, J.; Shi, Y.; Lammers, T.; Yu, H. J. Engineering nanoparticles to reprogram the tumor immune microenvironment for improved cancer immunotherapy. Theranostics2019, 9, 7981–8000.

    CAS  Google Scholar 

  200. Takikawa, O. Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated L-tryptophan metabolism. Biochem. Biophys. Res. Commun.2005, 338, 12–19.

    CAS  Google Scholar 

  201. Guzik, K.; Tomala, M.; Muszak, D.; Konieczny, M.; Hec, A.; Blaszkiewicz, U.; Pustula, M.; Butera, R.; Dömling, A.; Holak, T. A. Development of the inhibitors that target the PD-1/PD-L1 interaction—a brief look at progress on small molecules, peptides and macrocycles. Molecules2019, 24, 2071.

    CAS  Google Scholar 

  202. Shi, D. F.; An, X. L.; Bai, Q. F.; Bing, Z. T.; Zhou, S. Y.; Liu, H. X.; Yao, X. J. Computational insight into the small molecule intervening PD-L1 dimerization and the potential structure-activity relationship. Front. Chem.2019, 7, 764.

    CAS  Google Scholar 

  203. Skalniak, L.; Zak, K. M.; Guzik, K.; Magiera, K.; Musielak, B.; Pachota, M.; Szelazek, B.; Kocik, J.; Grudnik, P.; Tomala, M. et al. Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells. Oncotarget2017, 8, 72167–72181.

    Google Scholar 

  204. Sasikumar, P. G.; Ramachandra, R. K.; Adurthi, S.; Dhudashiya, A. A.; Vadlamani, S.; Vemula, K.; Vunnum, S.; Satyam, L. K.; Samiulla, D. S.; Subbarao, K. et al. A rationally designed peptide antagonist of the PD-1 signaling pathway as an immunomodulatory agent for cancer therapy. Mol. Cancer Ther.2019, 18, 1081–1091.

    CAS  Google Scholar 

  205. Musielak, B.; Kocik, J.; Skalniak, L.; Magiera-Mularz, K.; Sala, D.; Czub, M.; Stec, M.; Siedlar, M.; Holak, T. A.; Plewka, J. CA-170-a potent small-molecule PD-L1 inhibitor or not?. Molecules2019, 24, 2804.

    Google Scholar 

  206. Li, C. L.; Zhang, N. P.; Zhou, J. D.; Ding, C.; Jin, Y. Q.; Cui, X. Y.; Pu, K. F.; Zhu, Y. M. Peptide blocking of PD-1/PD-L1 interaction for cancer immunotherapy. Cancer Immunol. Res.2018, 6, 178–188.

    CAS  Google Scholar 

  207. Qian, Y.; Qiao, S.; Dai, Y. F.; Xu, G. Q.; Dai, B. L.; Lu, L. S.; Yu, X.; Luo, Q. M.; Zhang, Z. H. Molecular-targeted immunotherapeutic strategy for melanoma via dual-targeting nanoparticles delivering small interfering RNA to tumor-associated macrophages. ACS Nano2017, 11, 9536–9549.

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81860547, 81573008, 21671150, 21877084, 81171646, 31170776, and 21472139), the Science and Technology Commission of Shanghai Municipality (Nos. 14DZ2261100 and 15DZ1940106), the Fundamental Research Funds for the Central Universities (No. kx0150720173382) and the Joint Project of Health and Family Planning Committee of Pudong New Area (No. PW2017D-10).

Author information

Authors and Affiliations

  1. Breast cancer center, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai, 200120, China

    Jingxian Yang, Chunhui Wang, Shuo Shi & Chunyan Dong

Authors
  1. Jingxian Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunhui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuo Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunyan Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shuo Shi or Chunyan Dong.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, J., Wang, C., Shi, S. et al. Nanotechnologies for enhancing cancer immunotherapy. Nano Res. 13, 2595–2616 (2020). https://doi.org/10.1007/s12274-020-2904-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-020-2904-8

Keywords

Search

Navigation