Targeted Ultrasound Nanobubbles Therapy for Prostate Cancer via Immuno-Sonodynamic Effect

Abstract

Background

Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types.

Methods

This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs’ impact.

Results

The Ce6@aPD-L1 NBs effectively induced reactive oxygen species generation, leading to tumor cells death. In mice, they demonstrated a remarkable enhancement of immune responses compared to control groups. These immune responses encompassed immunogenic cell death induced by sonodynamic therapy and PD-1/PD-L1 blockade, activating dendritic cells maturation and effectively stimulating CD8+T cells.

Conclusion

Ce6@aPD-L1 NBs facilitate tumor-targeted delivery, activating anti-tumor effects through direct sonodynamic therapy action and immune system reactivation in the tumor microenvironment. Ce6@aPD-L1 NBs exhibit substantial potential for achieving synergistic anti-cancer effects in PCa.

Keywords:

• Ce6
• nanobubbles
• ultrasound
• sonodynamic therapy
• immunotherapy

Ethics Approval

This experiment was performed according to the Animal Ethics Committee of Renmin Hospital of Wuhan University (IACUC Issue No.20201103). In this study, we adhered to the ARRIVE guidelines and strictly followed the Regulations of the People’s Republic of China on the Administration of Laboratory Animals and its guiding principles for animal experiments. Our approach fully respected the lives of laboratory animals and aimed to minimize their suffering.

Acknowledgments

The authors greatly appreciated the support from the Central Laboratory and Animal Experiment Center of Renmin hospital of Wuhan University. This work was sponsored by the National Natural Science Foundation of China [Grant numbers 82271999].

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 report no conflicts of interest in this work.