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.
Conventional sonodynamic therapy (SDT) is unavoidably limited by the tumor microenvironment although many sonosensitizers have been developed to improve them to a certain extent. Given this, we propose a concept of sonocatalytic hydrogen evolution and define it as an oxygen-independent therapeutics. To demonstrate the feasibility of the concept, narrow-bandgap semiconductor bismuth sulfide (Bi2 S3 ) are selected as sonocatalysts and platinum (Pt) nanoparticles are grown in situ to optimize their catalytic performance. In this nanocatalytic system, Pt nanoparticles help to capture sono-excited electrons, whereas intratumoral overexpressed glutathione (GSH) as natural hole sacrificial agents can consume sono-excited holes, which greatly improves charge separation efficiency and promote the controllable and sustainable H2 generation. Even under hypoxic conditions, the Pt-Bi2 S3 nanoparticles can also produce sufficient H2 under US irradiation. Mechanistically, mitochondrial dysfunction caused by H2 and intratumoral redox homeostasis destruction by GSH depletion synergistically damage DNA to induce tumor cells apoptosis. At the same time, Pt nanoparticles and holes can also trigger the decomposition of hydrogen peroxide into O2 to relieve tumor hypoxia, thus synergistic with GSH depletion to reverse tumor immunosuppressive microenvironment. The proposed sonocatalysis mediated therapy will provide a new direction to realize facile and efficient cancer therapy. This article is protected by copyright. All rights reserved.