期刊
ACS CENTRAL SCIENCE
卷 6, 期 7, 页码 1208-1222出版社
AMER CHEMICAL SOC
DOI: 10.1021/acscentsci.9b01235
关键词
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资金
- National Basic Research Program of China [2015CB755500]
- National Natural Science Foundation of China [51933011, 31971296]
- Key Areas Research and Development Program of Guangzhou [202007020006]
- Natural Science Foundation of the Guangdong Province [2014A030312018]
Tumor-associated macrophages (TAMs) usually display the tumor-promoting M2 phenotype rather than the tumoricidal M1 phenotype. Thus, M2-to-M1 repolarization of TAMs has emerged as a promising strategy for tumor immunotherapy nowadays. However, immune side effects remain a great challenge, because phenotypic conversion of macrophages into the proinflammatory M1 phenotype may also be induced in normal tissue. Here, aiming at repolarizing TAMs without altering the M1/M2 polarization balance in healthy organs, we develop a micellar nanodrug with M2-targeting peptides (M2peptide) hidden in the pH-sheddable PEG corona so that an active targeting of M2-like macrophages is triggered only in the acidic tumor microenvironment (TME). The smart nanodrug effectively functions M2-to-M1 repolarization via M2-targeted codelivery of IKK beta siRNA and STAT6 inhibitor AS1517499 (AS), which suppresses the tumor growth and metastasis. Moreover, immune side effects are reduced because the neutral-pH environment in healthy organs does not trigger a stealth-to-nonstealth conversion of the nanodrug essential for M2-targeted drug delivery.
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