H2-Mediated Cancer Therapy with NIR-Driven Water SplittingScientific Research

Abstract:

As a newly emerging treatment strategy for many diseases, hydrogen therapy has attracted a lot of attention because of its excellent biosafety. However, high diffusivity and low solubility make it difficult to accumulate in the local lesions. Herein, we develop H2 self-generation nano-platform 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 exhibits high production capacity of H2 and active oxygen species (ROS), as well as appropriate photothermal conversion temperature. Furthermore, the rising temperature increases the Fenton reaction rate of Cu(I) with H2O2 and strengthens curative effect of chemodynamic therapy (CDT). The excess glutathione (GSH) in tumor microenvironment (TME) can deplete positive hole produced in valence band of g-C3N4 in g-C3N4/Cu3P Z-scheme heterojunction. GSH also can reduce Cu(II) to Cu(I), ensuring continuous Fenton reaction. Thus a NIR-driven H2 production nano-platform is constructed with H2 mediated cascade amplifying multimodal synergetic therapy.