Hybrid nanoparticle-mediated simultaneous ROS scavenging and STING activation improve the antitumor immunity of in situ vaccines
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Date
2024
Authors
Li, J.
Wu, T.
Wang, W.
Gong, Y.
Lu, M.
Zhang, M.
Lu, W.
Zhou, Y.
Yang, Y.
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Journal article
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Science Advances, 2024; 10(38):eadn3002-1-eadn3002-15
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Jianing Li, Tianze Wu, Weidong Wang, Yimin Gong, Mingzhu Lu, Mengmeng Zhang, Wanyue Lu, Yaming Zhou, Yannan Yang
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Abstract
In situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle-based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond-bridged organosilica nanoparticles, followed by coating with a Mn2+-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn2+ and SN38 comediated signaling and simultaneously scavenge preexisting H2O2 in the TME and Mn2+-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.
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© 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).