Journal
BIOMATERIALS
Volume 269, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2021.120670
Keywords
Macrophage; Living cell drug carrier; Cell surface modification; In situ activation; Immunotherapy
Funding
- National Natural Science Foundation of China [81801838, 82072064, 81971749]
- K.C.Wong Education Foundation [GJTD-2018-14]
- Natural Science Foundation of Guangdong Province [2018A030313013]
- Shenzhen Science and Technology Program [JCYJ20180302145912832, JCYJ20200109114616534]
- Guangdong Province National Science Fund [2020B1111540001]
- National Key Research and Development Program of China [2019YFE0198700]
- Zhuhai innovation and entrepreneurship team project [ZH01110405180056PWC]
- China Postdoctoral Science Foundation [2019M660219]
- Special Research Assistant Project of the Chinese Academy of Sciences [Y959101001]
- Guang dong Basic and Applied Basic Research Fund Project [2019A1515110222]
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The study utilized slow-release Poly I: C-encapsulated nanoparticles and biomimetic system MPLP to effectively inhibit tumor growth and metastasis by activating bone marrow-derived macrophages' tumor-specific immune response.
Immunotherapy is one of the most promising approaches to inhibit tumor growth and metastasis by activating host immune functions. However, the arising problems such as low immune response caused by complex tumor microenvironment and extremely systemic immune storm still limit the clinical applications of immunotherapy. Here, we construct Poly I: C-encapsulated poly (lactic-co-glycolic acid) nanoparticles (PLP NPs) with a slow release profile. A biomimetic system (MPLP), which loads PLP NPs on the surface of bone marrow-derived macrophage (BMDM) via the maleimide-thiol conjugation, is synthesized to effectively deliver PLP, control drug release and activate the tumor-specific immune response in situ. The results show that PLP NPs loading does not affect the activity and function of BMDM. Then, BMDM acts as a living cell drug vehicle and promotes the accumulation of PLP NPs in tumors, where Poly I: C is released from PLP NPs and reprograms BMDM into tumoricidal M1 macrophage. Furthermore, MPLP triggers potent antitumor immune responses in vivo and effectively inhibits local and metastatic tumors without causing adverse pathological immune reactions. This study offers an inspiration to facilitate clinical translation through the delivery of drugs by living immune cells for future anticancer therapy.
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