Novel PdPtCu Nanozymes for Reprogramming Tumor Microenvironment to Boost Immunotherapy Through Endoplasmic Reticulum Stress and Blocking IDO-Mediated Immune Escape

被引：33

作者：

Xie, Yulin ^{[1
]}

Wang, Man ^{[1
]}

Qian, Yanrong ^{[1
]}

Li, Lei ^{[1
]}

Sun, Qianqian ^{[1
]}

Gao, Minghong ^{[1
]}

Li, Chunxia ^{[1
]}

机构：

[1] Shandong Univ, Inst Mol Sci & Engn, Inst Frontier & Interdisciplinary Sci, Qingdao 266237, Peoples R China

来源：

SMALL | 2023年 / 19卷 / 44期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

combination therapy; endoplasmic reticulum targeting; immune checkpoint inhibitors; immunogenic cell death; noble metal nanozyme; IMMUNOGENIC CELL-DEATH; PHOTOTHERMAL THERAPY; NANOPARTICLES; METAL;

D O I：

10.1002/smll.202303596

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Breaking immunosuppressive tumor microenvironment (TME) has unique effects on inhibiting tumor growth and recurrence. Here, an endoplasmic reticulum (ER) targeted PdPtCu nanozyme (PNBCTER) is prepared to boost immunotherapy. First, PNBCTER has three kinds of enzyme activities, including catalase (CAT), glutathione oxidase (GSHOx), and peroxidase (POD)-like activities, which can reshape the TME. Second, PNBCTER kills tumor cells by photodynamic therapy (PDT) and photothermal therapy (PTT). Third, guided by T-ER, PNBCTER not only realizes the combination therapy of PDT, PTT and chemodynamic therapy (CDT), but also damages the ER of tumor cells and actives antitumor immune response, which breaks through the immune blockade of TME. Finally, the NLG919 blocks the tryptophan/kynurenine immune escape pathway and reverses the immunosuppressive TME. The strategy that reshaping the TME by enzyme catalysis and breaking immunosuppression provides a novel way for the application of combination therapy in tumor.

引用

页数：16