Affiliation:
1. Jiangsu Key Laboratory for Carbon‐Based Functional Materials and Devices Institute of Functional Nano and Soft Materials (FUNSOM) Soochow University 199 Ren'ai Road Suzhou Jiangsu 215123 P. R. China
2. Science and Technology Innovation Center Shandong First Medical University Jinan Shandong 250000 P. R. China
3. Jiangsu Key Laboratory for Molecular and Medical Biotechnology Cancer Institute Department of Biochemistry College of Life Science Nanjing Normal University Nanjing 210023 P. R. China
Abstract
AbstractTumor hypoxia and acidity, two general features of solid tumors, are known to have negative effect on cancer immunotherapy by directly causing dysfunction of effector immune cells and promoting suppressive immune cells inside tumors. Herein, a multifunctional colloidosomal microreactor is constructed by encapsulating catalase within calcium carbonate (CaCO3) nanoparticle‐assembled colloidosomes (abbreviated as CaP CSs) via the classic double emulsion method. The yielded CCaP CSs exhibit well‐retained proton‐scavenging and hydrogen peroxide decomposition performances and can thus neutralize tumor acidity, attenuate tumor hypoxia, and suppress lactate production upon intratumoral administration. Consequently, CCaP CSs treatment can activate potent antitumor immunity and thus significantly enhance the therapeutic potency of coloaded anti‐programmed death‐1 (anti‐PD‐1) antibodies in both murine subcutaneous CT26 and orthotopic 4T1 tumor xenografts. In addition, such CCaP CSs treatment also markedly reinforces the therapeutic potency of epidermal growth factor receptor expressing chimeric antigen receptor T (EGFR‐CAR‐T) cells toward a human triple‐negative breast cancer xenograft by promoting their tumor infiltration and effector cytokine secretion. Therefore, this study highlights that chemical modulation of tumor acidity and hypoxia can collectively reverse tumor immunosuppression and thus significantly potentiate both immune checkpoint blockade and CAR‐T cell immunotherapies toward solid tumors.
Funder
Collaborative Innovation Center of Suzhou Nano Science and Technology
Natural Science Foundation of Jiangsu Province
National Natural Science Foundation of China
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science