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

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 (CA...

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Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2023-11, Vol.19 (44), p.e2303596-n/a
Main Authors: Xie, Yulin, Wang, Man, Qian, Yanrong, Li, Lei, Sun, Qianqian, Gao, Minghong, Li, Chunxia
Format: Article
Language:English
Subjects:
Catalase
combination therapy
Endoplasmic reticulum
endoplasmic reticulum targeting
Glutathione
immune checkpoint inhibitors
Immune system
immunogenic cell death
Immunosuppression
Nanotechnology
noble metal nanozyme
Peroxidase
Tryptophan
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Summary: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 TER, 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. A novel PdPtCu nanozyme with multienzymic activities is synthesized, which not only reshapes the tumor microenvironment (TME) through enzyme catalysis, but also boosts immunotherapy through endoplasmic reticulum (ER) stress and blocking indoleamine 2, 3‐dioxygenase‐mediated immune escape. The strategy realizes ER‐targeted enzyme catalysis/photodynamic therapy/photothermal therapy/chemodynamic therapy/immunotherapy synergistic therapy and reverses the immunosuppressive TME.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.202303596