Abstract |
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 IKKβ 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.
|
Authors | Hong Xiao, Yu Guo, Bo Li, Xiaoxia Li, Yong Wang, Shisong Han, Du Cheng, Xintao Shuai |
Journal | ACS central science
(ACS Cent Sci)
Vol. 6
Issue 7
Pg. 1208-1222
(Jul 22 2020)
ISSN: 2374-7943 [Print] United States |
PMID | 32724855
(Publication Type: Journal Article)
|
Copyright | Copyright © 2020 American Chemical Society. |