All-in-one Cu-mediated Ag-assembled nanocomposites for photothermal-assisted photo/chemical dynamic therapy with hypoxia relief and enhanced reactive oxygen species

Abstract

Silver nanoparticles (AgNPs) have a wide adjustable absorption range. However, it is highly difficult to synthesize AgNPs with NIR absorption and act as an agent for photodynamic therapy (PDT) and photothermal therapy (PTT). Herein, we have fabricated an integrated agent (Ag@Cu) with broad NIR absorption, which alleviated hypoxia and enhanced reactive oxygen species (ROS), resulting in the improvement of PDT efficacy. The obtained Ag@Cu exhibited relatively mild PTT to alleviate hypoxia by accelerating blood flow in the tumor microenvironment and making more oxygenated hemoglobin reach the tumor microenvironment to provide oxygen, which enhanced the efficiency of PDT. The metal ions-mediated inorganic nanoparticle assembly approach of introducing Cu²⁺ achieved efficient chemodynamic therapy (CDT), amplifying the intracellular oxidative stress to further enhance the effects of PDT. Significantly, adenosine triphosphate (ATP) and excess glutathione (GSH) in tumor cells can also be depleted by copper ions, enhancing the efficacy of ROS-mediated therapy. Therefore, fabricating functional nanomaterials by highly efficient self-assembly strategies that introduce functional metal ions is a favorable method for multimodal tumor treatment.