Near-Infrared Responsive Membrane Nanovesicles Amplify Homologous Targeting Delivery of Anti-PD Immunotherapy against Metastatic Tumors.

Abstract

The major obstacles of anti-PD therapy in metastatic tumors are limited drug delivery in primary tumors and metastatic foci, and the lack of tumor-infiltrating lymphocytes (TILs). Here, the authors constructed a novel cellular membrane nanovesicles platform (M/IR NPs) based on homologous targeting and near-infrared (NIR) responsive release strategy to potentiate PD-1/PD-L1 blockade therapy against metastatic tumors. In tumor-bearing mice, biomimetic M/IR NPs targeted both primary tumors and their lung metastases. Upon laser irradiation, M/IR NPs reduced cancer-associated fibroblasts (CAFs) in tumor microenvironment, thus increasing the penetration of TILs. When shed from homologous tumor cell membranes, positively charged nanoparticles (IR NPs) core can capture released tumor-associated antigens, thereby enhancing the antigen-presenting ability of DCs to activate cytotoxic T lymphocytes. When the photothermal conversion temperature under NIR-laser is higher than 42 °C, M/IR NPs initiated the rupture of cell membranes and the responsive release of PD-1/PD-L1 inhibitor BMS, which significantly attenuated tumor-associated immunosuppression and synergistically induced T cellular immunity to inhibit the tumor growth and metastasis. Overall, biomimetic M/IR NPs can improve the targeting and therapeutic efficacy of anti-PD therapy in primary tumors and metastases, opening up a new avenue for the diagnosis and treatment of metastatic tumors in the future.

• Authors: Ya-Nan Tan, Jian-Dong Huang, Yong-Peng Li, Shan-Shan Li, Min Luo, Jie Luo, Anne Wing-Mui Lee, Li Fu, Fu-Qiang Hu, Xin-Yuan Guan
• Journal: Advanced healthcare materials (Adv Healthc Mater) Vol. 11 Issue 6 Pg. e2101496 (03 2022) ISSN: 2192-2659 [Electronic] Germany
• PMID: 34878725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Topics

• Animals
• Cell Line, Tumor
• Drug Delivery Systems
• Immunotherapy
• Mice
• Nanoparticles
• Neoplasms (drug therapy)
• Tumor Microenvironment