Synergistic Combination of an Intelligent Nanozyme and Radiotherapy for Treating Renal Cancer.

Background: Preserving nephrons while avoiding tumor recurrence during the treatment of renal cell carcinoma remains as a challenge in clinic. To achieve desired therapeutic outcome, we developed specific nanozymes based on the tumor microenvironment and evaluated its efficacy in combination with radiotherapy.

Methods: Herein, a hybrid nanozyme CeO@Au-PEG nanocomposite nanoparticle (NPs) was developed for the treatment of renal tumor. It was composed of gold nanozyme decorated CeO nanorods and exhibited both glucose-oxidase like by gold nanozyme and peroxidase-like catalytic activities. Due to the high metabolic rate of tumor cells, they take up a huge amount of glucose to survive and proliferate. Therefore, we generated CeO@Au-PEG NPs, which exhausted glucose in the tumor tissue and generated hydrogen peroxide, depleting the source of energy and causing tumor cell death. Then the generated hydrogen peroxide was degraded by the peroxidase-mimicking properties of CeO@Au-PEG NPs, elevating oxidative stress and thus enhancing tumor cell death. Moreover, due to the high mass nuclei of gold and cerium, they could further sensitize the tumors to radiotherapy and thus thoroughly eliminate tumors.

Results: With enough biocompatibility, CeO@Au-PEG NPs showed superior ability to deplete glucose as well as enhance oxidative stress by producing reactive oxygen species in RENCA cells under ionizing irradiation. Moreover, CeO@Au-PEG NPs greatly improved radiotherapy mediated tumor ablation in tumor bearing mice.

Conclusion: Systematic experiments demonstrated the synergistic therapeutic effects of the combination of CeO@Au-PEG NPs and radiotherapy in renal tumor model, which may serve as a promising strategy for treating renal cancer patients in the clinic.