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Cited 4 time in webofscience Cited 5 time in scopus
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Immunostimulation of tumor microenvironment by targeting tumor-associated macrophages with hypoxia-responsive nanocomplex for enhanced anti-tumor therapy SCIE SCOPUS

Title
Immunostimulation of tumor microenvironment by targeting tumor-associated macrophages with hypoxia-responsive nanocomplex for enhanced anti-tumor therapy
Authors
Kang, YeoulLim, JunhaSaravanakumar, GurusamyKim, JinseongPark, MihyeonIm, SooseokKim, Won Jong
Date Issued
2022-03-01
Publisher
Elsevier BV
Abstract
Tumor-associated macrophages (TAMs), which dampen the therapeutic efficacy of cancer immunotherapy, are the key players in the immunosuppressive tumor microenvironment (TME). Therefore, reprogramming TAMs into tumoricidal M1 macrophages possesses considerable potential as a novel immunotherapy. However, the low bioavailability of polarization agents and limited accumulation of TAMs restrict their anti-tumor efficacy. In this study, we developed a polymer-based hypoxia-responsive nanocomplex to target TAMs in hypoxia for enhanced cancer immunotherapy. We synthesized a hypoxia-cleavable polymer poly(ethylene glycol)-azo-poly(l-lysine) (PEG-azo-PLL) and formulated a nanocomplex by simple mixing PEG-azo-PLL and poly(I:C). By mimicking in vitro hypoxia conditions, PEG-azo-PLL/poly(I:C) complexes could transform the physicochemical properties to enhance the delivery efficiency of poly(I:C) to tumor hypoxia, where M2-like TAMs are accumulated. Furthermore, PEG-azo-PLL/poly(I:C) could successfully reduce the population of M2-like TAMs in hypoxic tumors and promoted infiltration of CD8+ T cells in vivo, resulting in the favorable conversion of immunosuppressive TME. Finally, PEG-azo-PLL/poly(I:C) could elicit a significant in vivo anti-tumor effect in B16F10-bearing mice in addition to a prolonged survival time, demonstrating that the hypoxia-responsive nanocomplex PEG-azo-PLL/poly(I:C) is a promising approach for TAM reprogramming immunotherapy for solid tumors.
URI
https://oasis.postech.ac.kr/handle/2014.oak/109307
DOI
10.1016/j.jconrel.2022.01.021
ISSN
0168-3659
Article Type
Article
Citation
Journal of Controlled Release, vol. 343, page. 78 - 88, 2022-03-01
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김원종KIM, WON JONG
Dept of Chemistry
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