Injectable hydrogel assisted formation of hydroxyl radical generating bioreactor enables photothermally enhanced chemodynamic and immunotherapy

Abstract

Photothermal therapy and chemodynamic therapy (CDT), two recently invented cancer treatments, have shown to be effective in potentiating immunotherapy through causing immunogenic cancer cell death. The rational integration of these two therapeutic modalities poses a formidable challenge in eliciting robust immunotherapy. Herein, an injectable hydrogel based bioreactor comprising of glucose oxidase (GOx), copper sulfide (CuS) nanoparticles, and poly (ethylene glycol) double acrylate (PEGDA) is prepared to potentiate immune checkpoint blockade (ICB) therapy. GOx can in situ convert glucose to hydrogen peroxide (H2O2) and gluconic acid, the latter of which further promotes the decomposition of H2O2 to hydroxyl radicals by creating an acidic microenvironment to benefit the pH-dependent Fenton-like catalytic reaction of Cu+, particularly in synergizing with near infrared (NIR) light exposure. Such catalytic couple of GOx and CuS together with NIR light exposure is efficient in inducing immunogenic cancer cell death. Additionally, GOx reprogrammed tumor immunosuppressive microenvironment by reducing lactate levels. Upon being fixed inside tumors with PEGDA hydrogel, such in situ formed bioreactor effectively suppresses the growth of 4T1 orthotopic murine breast cancers in Balb/c mice together with 808 nm laser exposure. Furthermore, such bioreactor enabled photothermally enhanced CDT could also synergize with anti-PD-L1 immunotherapy to more effectively suppress the growth of primary tumors and distant tumors. This study highlights that such NIR light and reactive oxygen species dual responsive bioreactor is robust to potentiate ICB immunotherapy.