NIR-Driven Water Splitting H₂ Production Nanoplatform for H₂-Mediated Cascade-Amplifying Synergetic Cancer Therapy

As a newly emerging treatment strategy for many diseases, hydrogen therapy has attracted a lot of attention because of its excellent biosafety. However, the high diffusivity and low solubility of hydrogen make it difficult to accumulate in local lesions. Herein, we develop a H₂ self-generation nanoplatform by in situ water splitting driven by near-infrared (NIR) laser. In this work, core-shell nanoparticles (CSNPs) of NaGdF₄:Yb,Tm/g-C₃N₄/Cu₃P (UCC) nanocomposites as core encapsulated with zeolitic imidazolate framework-8 (ZIF-8) modified with folic acid as shell are designed and synthesized. Due to the acid-responsive ZIF-8 shell, enhanced permeability and retention (EPR) effect, and folate receptor-mediated endocytosis, CSNPs are selectively captured by tumor cells. Upon 980 nm laser irradiation, CSNPs exhibit a high production capacity of H₂ and active oxygen species (ROS), as well as an appropriate photothermal conversion temperature. Furthermore, rising temperature increases the Fenton reaction rate of Cu(I) with H₂O₂ and strengthens the curative effect of chemodynamic therapy (CDT). The excess glutathione (GSH) in tumor microenvironment (TME) can deplete positive holes produced in the valence band of g-C₃N₄ in the g-C₃N₄/Cu₃P Z-scheme heterojunction. GSH also can reduce Cu(II) to Cu(I), ensuring a continuous Fenton reaction. Thus, a NIR-driven H₂ production nanoplatform is constructed for H₂-mediated cascade-amplifying multimodal synergetic therapy.