Journal
ADVANCED HEALTHCARE MATERIALS
Volume 9, Issue 13, Pages -Publisher
WILEY
DOI: 10.1002/adhm.202000064
Keywords
cancer immunotherapy; DNA nanotechnology; immunosuppression; STING activation; synergistic antitumor therapy
Funding
- National Natural Science Foundation of China [91859112, 21722503, 21874067]
- Natural Science Foundation of Jiangsu Province [BK20180340]
- 973 Program [2015CB659400]
- PAPD program
- Shuangchuang Program of Jiangsu Province
- Open Funds of the State Key Laboratory of Analytical Chemistry for Life Science [SKLACLS1704]
- Open Funds of the State Key Laboratory of Coordination Chemistry [SKLCC1819]
- Fundamental Research Funds for the Central Universities [021314380145]
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The promise of immunotherapy for cancer therapy has not been fully fulfilled because portions of tumors are immunosuppressive. To tackle this challenge, the initiation of immune system by stimulator of interferon genes (STING) pathway is explored and multifunctional STING-activating nanoparticles are rationally designed for synergistic antitumor therapy. The STING-activating nanoparticles have a formulation of Mn3O4@Au-dsDNA/DOX, where dsDNA is used to activate STING for immunotherapy and doxorubicin (DOX) is chosen as a model drug for chemotherapy. The STING-mediated immunity is activated, inducing interferon-beta (IFN-beta) production, increasing T cell priming, and enhancing effector T cell infiltration. Combined with chemotherapy, STING-mediated immunotherapy shows good antitumor efficacy by inhibiting tumor growth and prolonging survival rate in vivo. The promise of cancer immunotherapy can be fulfilled by combining novel antitumor immunity with innovative nanotechnology, and chemotherapy and targeted therapies.
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