Tumor-targeted biocatalyst with self-accelerated cascade reactions for enhanced synergistic starvation and photodynamic therapy

Abstract

Combination therapy has been considered as an attractive strategy in complementary anticancer treatment. However, its therapeutic outcomes could be inhibited by the tumor microenvironment (TME) such as hypoxia and insufficient endogenous hydrogen peroxide concentration. Herein, we typically design a multilayered porous biocatalyst (USCGP) realizing cascade reactions-enhanced synergistic cancer therapy. Glucose oxidase (GOD) loaded on USCGP catalyzes glucose decomposition accompanied by regulating TME, which activates double enzyme-like catalysis of USCGP. Concurrently, the cascade reactions between GOD and cerium oxide (CeO2) not only promote nutrition consumption but also enhance the generation of hydroxyl radicals (•OH). In addition, under near-infrared (NIR) laser excitation, upconversion nanoparticles (UCNPs) in the core could convert NIR light to UV emission to trigger photocatalysis reactions of CeO2, achieving efficient spatio-temporal controllable photodynamic therapy. In particular, the modification of poly(ethylene glycol)-cyclo (Arg-Gly-Asp-d-Phe-Lys) (NH2-PEG1000-cRGDfK, abbreviated as PEG-cRGDfK) facilitates the accumulation of USCGP into tumor cells. Furthermore, USCGP could also be served as excellent contrast agent for computed tomography (CT) imaging in tumor diagnosis. Taken together, USCGP exhibits high-performance in tumor suppression with minimal side effects in vitro and in vivo, realizing additive cooperation of long-term starvation and robust photodynamic treatment strategy.