Multichannel Immune Nanoregulators Suppress Lactic Acid Metabolism and Lactic Acid‐Shaped Acidic Microenvironment to Uproot Anti‐Tumor Immunosuppression
Abstract
Abstract Lactic acid (LA) itself and the LA‐shaped acidic tumor microenvironment (TME) are identified as root causes of cancer immunosuppression, and no effective strategies address them. Here a multichannel immune nanoregulator is engineered to dampen acidic TME and repolarize non‐inflammatory macrophages to uproot this source of cancer immunosuppression, wherein fluorocarbon chains (FC)‐modified mesoporous silica (FM) serves as nanoreactors and carriers to in situ synthesize CaO 2 and load R848, respectively, followed by liposome coating, anti‐CD105 modification and FC‐mediated O 2 binding in sequence. Both liposome shell and intraparticle FC ensure safe CaO 2 delivery. Ultrasound‐triggered FC‐binding O 2 burst and liposomes‐destruction‐enhanced CaO 2 reactions with H + and H 2 O produce O 2 . This process depletes pre‐existing H + and inhibits glycolysis LA production to cut off acidic TME source, and uproots their actions in reshaping cancer immunosuppression, e.g., removing the polarization impetus toward non‐inflammatory M2 ones, addressing both symptoms and root causes of cytotoxic T lymphocytes and PD1+ T cells inactivation, etc. The cancer immunosuppression uprooting encourages the anti‐tumor efficacy of cancer calcification and intratumoral H 2 O 2 accumulation in the immune nanoregulators especially after anti‐CD105‐mediated active targeting accumulation. Collectively, this work presents a solution to uproot LA and non‐inflammatory macrophages‐induced cancer immunosuppression.
Article Details
Authors (12)
Chao Fang
State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering & Institute of Artificial Intelligence & Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM)
Qiuxia Peng
Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China
Xiaoying Li
Xiao Qu
Zi Qiao
Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China
Binxu Yin
Lujia Xiao
Department of Orthopedics Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China Chengdu Sichuan China
Yi Chen
Xiulin Dong
Lulu Cai
Department of Orthopedics and Central Laboratory Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China No. 32, West Second Section, First Ring Road Chengdu Sichuan 610072 China
Litao Sun
School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University
Kun Zhang