Dual‐Pronged Attack: pH‐Driven Membrane‐Anchored NIR Dual‐Type Nano‐Photosensitizer Excites Immunogenic Pyroptosis and Sequester Immune Checkpoint for Enhanced Prostate Cancer Photo‐Immunotherapy

Autor: He Wang, Zhangxin He, Yijian Gao, Dexiang Feng, Xuedong Wei, Yuhua Huang, Jianquan Hou, Shengliang Li, Weijie Zhang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Advanced Science, Vol 10, Iss 28, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202302422
Popis: Abstract Prostate cancer (PCa) is a frustrating immunogenic “cold” tumor and generally receives unsatisfied immunotherapy outcomes in the clinic. Pyroptosis is an excellent immunogenic cell death form that can effectively activate the antitumor immune response, promote cytotoxic T‐lymphocyte infiltration, and convert tumors from “cold” to “hot.” However, the in vivo application of pyroptosis drugs is seriously limited, and the upregulation of tumor PD‐L1 caused by photo‐immunotherapy further promotes immune escape. Herein, a new nano‐photosensitizer (YBS‐BMS NPs‐RKC) with pH‐response integrating immunogenic pyroptosis induction and immune checkpoint blockade is developed. The pH‐responsive polymer equipped with the cell membrane anchoring peptide RKC is used as the carrier and further encapsulated with the near‐infrared‐activated semiconductor polymer photosensitizer YBS and a PD‐1/PD‐L1 complex small molecule inhibitor BMS‐202. The pH‐driven membrane‐anchoring and pyroptosis activation of YBS‐BMS NPs‐RKC is clearly demonstrated. In vitro and in vivo studies have shown that this dual‐pronged therapy stimulates a powerful antitumor immune response to suppress primary tumor progression and evokes long‐term immune memory to inhibit tumor relapse and metastasis. This work provides an effective self‐synergistic platform for PCa immunotherapy and a new idea for developing more biocompatible photo‐controlled pyroptosis inducers.
Databáze: Directory of Open Access Journals
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