Repolarizing tumor-associated macrophages by layered double hydroxide-based deacidification agent for tumor chemodynamic therapy and immunotherapy

作者全名："Chen, Chunmei; Zhang, Wei; Lu, Shi-Yu; Wang, Jingjing; Tan, Yixin; Zhao, Sheng; Ouyang, Yi; Xu, Luen; Zhou, Benqing; Yin, Xuntao; Ran, Haitao; Liu, Hui"

作者地址："[Chen, Chunmei; Wang, Jingjing; Tan, Yixin; Zhao, Sheng; Ouyang, Yi; Xu, Luen; Liu, Hui] Southwest Univ, Sch Mat & Energy, 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; [Lu, Shi-Yu] Chongqing Univ Sci & Technol, Coll Met & Mat Engn, Chongqing 401331, Peoples R China; [Yin, Xuntao] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangdong Prov Clin Res Ctr Child Hlth, Dept Radiol, Guangzhou 510623, Peoples R China; [Zhou, Benqing] Shantou Univ, Coll Engn, Dept Biomed Engn, Shantou 515063, Peoples R China"

通信作者："Liu, H (通讯作者)，Southwest Univ, Sch Mat & Energy, 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.; Yin, XT (通讯作者)，Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangdong Prov Clin Res Ctr Child Hlth, Dept Radiol, Guangzhou 510623, Peoples R China.; Zhou, BQ (通讯作者)，Shantou Univ, Coll Engn, Dept Biomed Engn, Shantou 515063, Peoples R China."

来源：COLLOIDS AND SURFACES B-BIOINTERFACES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000993773200001

JCR分区：Q1

影响因子：5.8

年份：2023

卷号：223

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Deacidification agent; Macrophage repolarization; Immune activation; Tumor microenvironment; Chemodynamic therapy

摘要："Tumor-associated macrophages (TAMs)-mediated immunotherapy has attracted extensive attention in tumor elimination. However, the acidic tumor microenvironment (TME) severely limits the phenotype of TAMs to pro-tumoral M2 state, suppressing immune response efficacy against tumors. Herein, novel poly(acrylic acid) (PAA)-coated, doxorubicin (DOX)-loaded layered double hydroxide (LDH) nanosheets (NSs) were developed as deacidification agent to repolarize TAMs from pro-tumoral M2 to anti-tumoral M1 phenotype for tumor elimi-nation through combined chemodynamic therapy and immunotherapy. When located in tumor regions, LDH-PAA@DOX NSs display good deacidification capacity to neutralize acidic TME, achieving the repolarization of TAMs to M1 phenotype and further activating CD8+ T cells. During the deacidification process, these NSs are acid-responsive and degrade to release Fe3+ and DOX. The former can be reduced to Fe2+ by intracellular glutathione, meanwhile disrupting the antioxidant defense system of tumor cells. The latter can damage tumor cells directly and further stimulate the production of hydrogen peroxide, providing abundant substrate for the Fenton reaction. Toxic hydroxyl radical is excessively produced through Fe2+-mediated Fenton reaction to cause intratumoral oxidative stress. In vivo data revealed that significant tumor elimination can be achieved under LDH-PAA@DOX treatment. This work not only provides a promising paradigm for neutralizing acidic TME using deacidification agent but also highlights the effectiveness of combined chemodynamic therapy and immuno-therapy in tumor treatment."

基金机构："National Natural Science Foundation of China [51703184, 82071926, 92168106]; Natural Science Foundation of Guangdong Province [2021A1515010441]; Young Elite Scientists Sponsorship Program by CAST [CSTB2022NSCQ-MSX0557]; Natural Science Foundation of Chongqing [ckrc2021050]; Talent Introduction of Chongqing University of Science and Technology [2020LKSFG05C]; Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices; 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant; [2021QNRC001]"

基金资助正文："This research was funded by the National Natural Science Foundation of China (51703184, 82071926, 92168106), the Natural Science Foundation of Guangdong Province (2021A1515010441), and 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant (2020LKSFG05C), Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0557), Talent Introduction of Chongqing University of Science and Technology (ckrc2021050). This research was also supported by Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices."