期刊
NANO LETTERS
卷 21, 期 10, 页码 4231-4240出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c00209
关键词
nanoparticles; Escherichia coli; tumor-associated macrophages; polarization; immunogenic cell death
类别
资金
- National Natural Science Foundation of China [51725303, 52033007, 52073236]
- 5th Chinese Association for Science and Technology Young Talents Support Project
A new cancer treatment strategy has been developed, where tumor-associated macrophage polarization therapy combined with ICD induced by low-dose chemotherapy drugs can significantly enhance the efficacy of immunotherapy.
The tumor immunosuppressive microenvironment greatly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the tumor microenvironment, which can inhibit the tumor after converting it to an M1-like phenotype. In addition, immunogenic cell death (ICD) can increase the amount of T lymphocytes in tumors, activating antineoplastic immunity. Herein, tumor-associated macrophage polarization therapy supplemented with PLGA-DOX (PDOX)-induced ICD is developed for cancer treatment. The nanoparticles/bacteria complex (Ec-PR848) is fabricated for tumor targeting and TAM polarization, and PLGA-R848 (PR848) are attached to the surface of Escherichia coli (E. coli) MG1655 via electrostatic absorption. The toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and E. coli can greatly polarize M2 macrophages to M1 macrophages, while PDOX-induced ICD can also impair the immunosuppression of the tumor microenvironment. This strategy shows that tumor-associated macrophage polarization therapy combined with ICD induced by low-dose chemotherapeutic drugs can commendably enhance the efficacy of immunotherapy.
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