This study demonstrates that NIR-activated CoP/NiCoP nanoadjuvants combined with lactate metabolism inhibition can effectively suppress tumor proliferation and metastasis through enhanced photocatalytic hydrogen production and potentiated immune activation. By simultaneously depleting immunosuppressive lactic acid and inducing mitochondrial dysfunction, this metabolism-regulated approach offers a novel therapeutic paradigm with improved safety profile for cancer treatment.
Plain-Language Summary
Researchers designed a nanoparticle (tiny engineered particle) that activates when exposed to near-infrared light and produces hydrogen gas while also blocking lactic acid—a substance that helps tumors hide from the immune system. In laboratory tests, this combination approach reduced tumor growth by simultaneously boosting immune attack, generating reactive molecules that damage cancer cells, and disrupting cancer cell energy production. The study was conducted in cells and animal models, not humans.
Abstract
Near-infrared (NIR) laser-induced photoimmunotherapy has aroused great interest due to its intrinsic non-invasiveness and spatiotemporal precision, while immune evasion evoked by lactic acid (LA) accumulation severely limits its clinical outcomes. Although several metabolic interventions have been devoted to ameliorate immunosuppression, intracellular residual LA still remains a potential energy source for oncocyte proliferation. Herein, we construct an immunomodulatory nanoadjuvant based on a yolk-shell CoP/NiCoP (CNCP) heterostructure loaded with the monocarboxylate transporter 4 (MCT4) inhibitor fluvastatin sodium (Flu) to concurrently relieve immunosuppression and elicit robust antitumor immunity. Under NIR irradiation, CNCP heterojunctions exhibit superior photothermal performance and photocatalytic production of reactive oxygen species (ROS) and hydrogen. The continuous heat then facilitates Flu release to restrain LA exudation from tumor cells, whereas cumulative LA can be depleted as a hole scavenger to improve photocatalytic efficiency. Subsequently, potentiated photocatalytic therapy (PCT) can not only initiate systematic immunoreaction, but also provoke severe mitochondrial dysfunction and disrupt the energy supply for heat shock protein (HSP) synthesis, in turn realizing mild photothermal therapy (PTT). Consequently, LA metabolic remodeling endows an intensive cascade treatment with an optimal safety profile to effectually suppress tumor proliferation and metastasis, which offers a new paradigm for the development of metabolism-regulated immunotherapy. This article is protected by copyright. All rights reserved.
