Affiliation:
1. Institute of Molecular Sciences and Engineering Institute of Frontier and Interdisciplinary Science Shandong University Qingdao 266237 P. R. China
2. Shenzhen Key Laboratory of Polymer Science and Technology Guangdong Research Center for Interfacial Engineering of Functional Materials College of Materials Science and Engineering Shenzhen University Shenzhen 518055 P. R. China
Abstract
AbstractTraditionally referred to as “metabolic junk”, lactate has now been recognized as essential “energy currency” and crucial “messenger” that contributes to tumor evolution, immunosuppression, etc., thus presenting a promising strategy for antitumor interventions. Similarly, kynurenine (Kyn) also exerts an immunosuppressive function, thereby significantly compromising the effectiveness of immunotherapy. This study proposes and validates a strategy for enhancing immunotherapy through photothermal‐assisted depletion of lactate sustained by cycle‐like O2 supply, with blocking the tryptophan (Trp)/Kyn metabolic pathway. In brief, a nanozyme therapeutic agent (PNDPL) is constructed, which mainly consists of PtBi nanozymes, lactate oxidase (LOX) and the indoleamine 2,3‐dioxygenase (IDO) inhibitor NLG919. The PtBi nanozymes, which exhibit a catalase (CAT)‐like activity, form a positive feedback loop with LOX to consume lactate while self‐supplying O2. Moreover, PtBi nanozymes retain enzyme‐like performance even in a slightly acidic tumor microenvironment. Under 1064 nm irradiation, photothermal therapy (PTT) not only induces tumor cell death but also accelerates lactate exhaustion. Therefore, the combination of lactate depletion‐induced starvation therapy and PTT, along with the blocking of IDO‐mediated immune escape, effectively inhibits tumor growth and reverses immunosuppressive microenvironment, thus preventing tumor metastasis. This study represents the first investigation into the synergistic antitumor effects by lactate metabolism regulation and IDO‐related immunotherapy.
Funder
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Postdoctoral Innovation Project of Shandong Province
Natural Science Foundation of Shandong Province
Taishan Scholar Project of Shandong Province
Subject
General Materials Science,General Chemistry
Cited by
4 articles.
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