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

Abstract

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 CeO₂@Au-PEG nanocomposite nanoparticle (NPs) was developed for the treatment of renal tumor. It was composed of gold nanozyme decorated CeO₂ 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 CeO₂@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 CeO₂@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, CeO₂@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, CeO₂@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 CeO₂@Au-PEG NPs and radiotherapy in renal tumor model, which may serve as a promising strategy for treating renal cancer patients in the clinic.

Keywords:

• nanozyme
• radiotherapy
• glucose consumption
• reactive oxygen species
• renal cell carcinoma

Acknowledgment

All animal procedures were performed in accordance with the protocol approved by the Ethics Committee of Laboratory Animal of Henan Provincial Chest Hospital ((Document No. 04-04 of 2021, Animal Ethics Committee). All animal experiments were in accordance with the animal ethics guidelines of the Animal Care and Use Committee of the Laboratory Animal Science Department of Henan Provincial Chest Hospital.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflict of interest.

Additional information

Funding

This research was funded by Joint Project of Medical Science and Technology of Henan Province (No. LHGJ20220842).