Ultrasmall Bi/Cu Coordination Polymer Combined with Glucose Oxidase for Tumor Enhanced Chemodynamic Therapy by Starvation and Photothermal Treatment

Multi-modal combination therapy for tumor is expected to have superior therapeutic effect compared with monotherapy. In this study, a super-small bismuth/copper-gallic acid coordination polymer nanoparticle (BCN) protected by polyvinylpyrrolidone is designed, which is co-encapsulated with glucose oxidase (GOX) by phospholipid to obtain nanoprobe BCGN@L. It shows that BCN has an average size of 1.8 +/- 0.7 nm, and photothermal conversion of BCGN@L is 31.35% for photothermal imaging and photothermal therapy (PTT). During the treatment process of 4T1 tumor-bearing nude mice, GOX catalyzes glucose in the tumor to generate gluconic acid and hydrogen peroxide (H2O2), which reacts with copper ions (Cu2+) to produce toxic hydroxyl radicals (center dot OH) for chemodynamic therapy (CDT) and new fresh oxygen (O2) to supply to GOX for further catalysis, preventing tumor hypoxia. These reactions increase glucose depletion for starvation therapy , decrease heat shock protein expression, and enhance tumor sensitivity to low-temperature PTT. The in vitro and in vivo results demonstrate that the combination of CDT with other treatments produces excellent tumor growth inhibition. Blood biochemistry and histology analysis suggests that the nanoprobe has negligible toxicity. All the positive results reveal that the nanoprobe can be a promising approach for incorporation into multi-modal anticancer therapy. A super-small bismuth/copper-gallic acid coordination polymer nanoparticle presents good abilities of photothermal-treatment combined with glucose oxidase for chemodynamic-starvation therapy in vivo. The approximate to 2nm Bi and Cu in the depolymerized nanoparticle can be released and flowed through the kidney with the blood. The probe can be used in real-time monitoring or precision treatment of tumor in vivo through EPR effect.image