Proton Sponge Nanocomposites for Synergistic Tumor Elimination via Autophagy Inhibition-Promoted Cell Apoptosis and Macrophage Repolarization-Enhanced Immune Response

作者全名："Duan, Yifan; Zhang, Wei; Ouyang, Yi; Yang, Qiang; Zhang, Qiuye; Zhao, Sheng; Chen, Chunmei; Xu, Ting; Zhang, Qun; Ran, Haitao; Liu, Hui"

作者地址："[Duan, Yifan; Ouyang, Yi; Yang, Qiang; Zhang, Qiuye; Zhao, Sheng; Chen, Chunmei; Xu, Ting; Liu, Hui] Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China; [Zhang, Wei; Ran, Haitao] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China; [Zhang, Qun; Liu, Hui] Southern Med Univ, Guangdong Prov Key Lab Bone & Joint Degenerat Dis, Off Clin Trial Drug, Affiliated Hosp 3, Guangzhou 510630, Peoples R China"

通信作者："Liu, H (通讯作者)，Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China.; Ran, HT (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing 400010, Peoples R China.; Zhang, Q; Liu, H (通讯作者)，Southern Med Univ, Guangdong Prov Key Lab Bone & Joint Degenerat Dis, Off Clin Trial Drug, Affiliated Hosp 3, Guangzhou 510630, Peoples R China."

来源：ACS APPLIED MATERIALS & INTERFACES

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001193617200001

JCR分区：Q1

影响因子：8.3

年份：2024

卷号：16

期号：14

开始页：17285

结束页：17299

文献类型：Article

关键词：proton sponge; autophagy inhibition; macrophagerepolarization; dendrimer; synergistic tumor treatment

摘要："Cytoprotective autophagy and an immunosuppressive tumor microenvironment (TME) are two positive promoters for tumor proliferation and metastasis that severely hinder therapeutic efficacy. Inhibiting autophagy and reconstructing TME toward macrophage activation simultaneously are of great promise for effective tumor elimination, yet are still a huge challenge. Herein, a kind of dendrimer-based proton sponge nanocomposites was designed and constructed for tumor chemo/chemodynamic/immunotherapy through autophagy inhibition-promoted cell apoptosis and macrophage repolarization-enhanced immune response. These obtained nanocomposites contain a proton sponge G5AcP dendrimer, a Fenton-like agent Cu(II), and chemical drug doxorubicin (DOX). When accumulated in tumor regions, G5AcP can act as an immunomodulator to realize deacidification-promoted macrophage repolarization toward antitumoral type, which then secretes inflammatory cytokines to activate T cells. They also regulate intracellular lysosomal pH to inhibit cytoprotective autophagy. The released Cu(II) and DOX can induce aggravated damage through a Fenton-like reaction and chemotherapeutic effect in this autophagy-inhibition condition. Tumor-associated antigens are released from these dying tumor cells to promote the maturity of dendritic cells, further activating T cells. Effective tumor elimination can be achieved by this dendrimer-based therapeutic strategy, providing significant guidance for the design of a promising antitumor nanomedicine."

基金机构：National Natural Science Foundation of China [82071926]; National Natural Science Foundation of China [CSTB2023NSCQ-MSX0149]; Natural Science Foundation of Chongqing [KJZD-K202300403]; Science and Technology Research Program of Chongqing Municipal Education Commission [202201011600]; Basic and Applied Basic Research Project of Guangzhou Basic Research Program

基金资助正文："This research was funded by the National Natural Science Foundation of China (82071926), the Natural Science Foundation of Chongqing (CSTB2023NSCQ-MSX0149), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJZD-K202300403), and the Basic and Applied Basic Research Project of Guangzhou Basic Research Program (202201011600)."