A component-optimized chemo-dynamic nanoagent for enhanced tumour cell-selective chemo-dynamic therapy with minimal side effects in a glioma mouse model

Abstract

Although CuO-deposited bovine serum albumin (CuO-BSA) and glucose oxidase (GOx) were combined to achieve H₂O₂ self-supplied chemo-dynamic therapy (CDT) and glucose consumption-based starvation therapy, the uses of copper and GOx have not been optimized to enhance tumour-selective reactive oxygen species (ROS) generation and minimize toxicity to normal cells as well. Here, chemo-dynamic nanoparticles (CBGP NPs) were prepared through a facile biomineralization process and subsequent coatings with GOx and the cationic polymer PEG_2k-PEI_1.8k. Through optimizing the use of copper, GOx, and PEG_2k-PEI_1.8k, the CBGP NPs showed high cellular uptake efficiency, enhanced tumour-selective ROS generation, and minimal side effects toward normal cells. The CBGP NP-mediated glucose consumption, GSH-depletion, and ˙OH generation synergistically induced tumour cell apoptosis both in vitro and in vivo. It is believed that the optimized CBGP NPs can be a promising nanoplatform for effective tumour therapy with minimal side effects.