Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy  

作　　者：Siqin He Lulu Wang Dongxu Wu Fan Tong Huan Zhao Hanmei Li Tao Gong Huile Gao Yang Zhou 

机构地区：[1]Key Laboratory of Tropical Biological Resources of Ministry of Education,School of Pharmaceutical Sciences,Hainan University,Haikou 570200,China [2]Key Laboratory of Drug-Targeting and Drug Delivery System,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [3]Revvity Inc.,Waltham,MA 02451,USA [4]School of Food and Biological Engineering,Chengdu University,Chengdu 610106,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第2期765-780,共16页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82173762,China);the Key Research and Development Program of Science and Technology Department of Sichuan Province(2022JDJQ0050,China);the Fundamental of Research Funds for the Central Universities.

摘　　要：A major challenge facing photodynamic therapy(PDT) is that the activity of the immuneinduced infiltrating CD8^(+)T cells is subject to the regulatory T lymphocytes(Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment(TME), a supramolecular photodynamic nanoparticle(DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin(DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration(Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs.The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

关 键 词：Photodynamic therapy Immunosuppressive microenvironment IMMUNOMODULATOR Dual-responsive Supramolecularassembly Checkpointblockade 

分 类 号：R943[医药卫生—药剂学]