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Journal of Controlled Release

Journal of Controlled Release

IF: 10.5
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Targeting glutamine metabolism with photodynamic immunotherapy for metastatic tumor eradication

Published:1 May 2023 DOI: 10.1016/j.jconrel.2023.04.027 PMID: 37068523
Linping Zhao , Xiaona Rao , Rongrong Zheng , Chuyu Huang , Renjiang Kong , Xiyong Yu , Hong Cheng , Shiying Li

Abstract

Immune checkpoint blockade (ICB) has shown significant clinical success, yet its responses can vary due to immunosuppressive tumor microenvironments. To enhance antitumor immunity, combining ICB therapy with tumor metabolism reprogramming may be a promising strategy. In this study, we developed a photodynamic immunostimulant called BVC aiming to boost immune recognition and prevent immune escape for metastatic tumor eradication by reprogramming glutamine metabolism. BVC, a carrier free self-assembled nanoparticle, comprises a photosensitizer (chlorin e6), an ASCT2 inhibitor (V9302) and a PD1/PDL1 blocker (BMS-1), offering favorable stability and enhanced drug delivery efficiency. The potent photodynamic therapy (PDT) capability of BVC is attributed to its regulation of glutamine metabolism, which influences the redox microenvironment within tumor tissues. By targeting ASCT2-mediated glutamine metabolism, BVC inhibits glutamine transport and GSH synthesis, leading to the upregulation of Fas and PDL1. Additionally, BVC-mediated PDT induces immunogenic cell death, triggering a cascade of immune responses. Consequently, BVC not only enhances immune recognition between CD8+ T cells and Fas-overexpressing tumor cells but also reduces tumor cell immune escape through PD1/PDL1 blockade, significantly benefiting metastatic tumor eradication. This study paves a novel approach for multi-synergistic tumor treatment.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
V-9302 1855871-76-9 C34H38N2O4 88 suppliers $25.00-$5210.50
V-9302 1855871-76-9 C34H38N2O4 88 suppliers $25.00-$5210.50
V-9302 1855871-76-9 C34H38N2O4 88 suppliers $25.00-$5210.50
V-9302 1855871-76-9 C34H38N2O4 88 suppliers $25.00-$5210.50

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