Tumor microenvironment remodeling via targeted depletion of M2-like tumor-associated macrophages for cancer immunotherapy

作者全名："Cao, Yi; Qiao, Bin; Chen, Qiaoqi; Xie, Zhuoyan; Dou, Xiaoyun; Xu, Lihong; Ran, Haitao; Zhang, Liang; Wang, Zhigang"

作者地址："[Cao, Yi; Qiao, Bin; Chen, Qiaoqi; Ran, Haitao; Zhang, Liang; Wang, Zhigang] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, State Key Lab Ultrasound Med & Engn, Chongqing 400010, Peoples R China; [Xie, Zhuoyan] Chongqing Gen Hosp, Dept Ultrasound, Chongqing 401122, Peoples R China; [Dou, Xiaoyun; Xu, Lihong] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Zhang, Liang] Chongqing Med Univ, Affiliated Hosp 1, Dept Ultrasound, Chongqing 400042, Peoples R China"

通信作者："Zhang, L; Wang, ZG (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, State Key Lab Ultrasound Med & Engn, Chongqing 400010, Peoples R China.; Zhang, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Ultrasound, Chongqing 400042, Peoples R China."

来源：ACTA BIOMATERIALIA

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000955561200001

JCR分区：Q1

影响因子：9.4

年份：2023

卷号：160

期号：　

开始页：239

结束页：251

文献类型：Article

关键词：Tumor-associated macrophages; Immunosuppressive tumor; microenvironment; Cancer immunotherapy; Sonodynamic therapy

摘要："M2-like tumor-associated macrophages (TAMs) typically exhibit numerous tumor-promoting properties. Reducing the abundance of M2-like TAMs would shed light on the relief of immunosuppressive tumor microenvironment (TME), activation of the host immune system, infiltration of CD8+ T cells into the TME and restoring the function of the infiltrating T cells, which collectively inhibits tumor growth. Therefore, targeted depletion of M2-like TAMs can be a promising immunotherapy approach. In this study, we ra-tionally constructed an M2-like TAMs-targeted nanoliposome, which encapsulates zoledronic acid (ZA) in the core, loads hematoporphyrin monomethyl ether (HMME, a typical sonosensitizer) in the lipid bi-layer, and modifies M2pep peptide (the targeting unit) on the surface (designated as M-H@lip-ZA). Our aim is to validate the effectiveness of M-H@lip-ZA nanoliposomes to remodel TME via targeted depletion of M2-like TAMs for cancer immunotherapy. Through the M2pep peptide, M-H@lip-ZA can be efficiently delivered to M2-like TAMs. In the meantime, reactive oxygen species (ROS) resulting from sonodynamic therapy (SDT), together with inner ZA that shows high affinity and cytotoxicity to TAMs, can effectively deplete M2-like TAMs and remodel TME (normalize tumor vasculatures, strengthen intertumoral perfu-sion, ease tumor hypoxia, increase immune-promoting cytokines and decrease immunosuppressive cy-tokines). The tumor growth can be effectively inhibited. This work proposed a new paradigm for cancer immunotherapy via targeted depletion of M2-like TAMs.Statement of Significance center dot M2-like TAMs-targeted nanoliposome (M-H@lip-ZA) was designed and prepared.center dot Sonodynamic therapy (SDT), together with zoledronic acid (ZA) that shows high affinity and cy-totoxicity to tumor-associated macrophages (TAMs), can effectively deplete M2-like TAMs. Subsequently, immune-promoting tumor microenvironment (TME) can be formed, which includes normalized tumor vasculatures, enhanced intertumoral perfusion, relieved tumor hypoxia, increased immune-promoting cy-tokines, and decreased immunosuppressive cytokines.center dot The targeted depletion of M2-like TAMs is a promising cancer immunotherapy approach.(c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved."

基金机构："National Natural Science Foundation of China [82172092]; Key Project of Application Development Plan of Chongqing [cstc2019jscx-dxwtBX0004]; China Postdoctoral Science Foundation [2021TQ0394, 2021M00637]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (Grant No. 82172092); Key Project of Application Development Plan of Chongqing (Grant No. cstc2019jscx-dxwtBX0004). The authors also appreciate the China Postdoctoral Science Foundation (Grant No. 2021TQ0394, 2021M00637), and the Chongqing Postdoctoral Program for Innovative Talents."