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Targeted Ultrasound Nanobubbles Therapy for Prostate Cancer via Immuno-Sonodynamic Effect
Xin Huang1, Yueying Chen1, Fanglu Zhong1
1Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
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.
Insights
This study developed novel nanobubbles (NBs) encapsulating chlorin e6 and anti-PD-L1 antibodies for prostate cancer (PCa). These nanobubbles show promise in enhancing anti-tumor immunity and sonodynamic therapy for PCa treatment.
Area of Science:
- Oncology
- Nanotechnology
- Immunotherapy
Background:
- Prostate cancer (PCa) is a major global health concern.
- Current immunotherapy, specifically anti-PD-L1 antibody (Ab) therapy, has shown limited efficacy in PCa.
- There is a need for novel therapeutic strategies to improve PCa treatment outcomes.
Purpose of the Study:
- To develop and evaluate novel lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab for PCa treatment.
- To assess the efficacy of these nanobubbles in inducing anti-tumor effects via sonodynamic therapy and immune system activation.
- To investigate the potential of these nanobubbles for synergistic anti-cancer effects in the tumor microenvironment.
Main Methods:
- Lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs) were synthesized using the thin film hydration method.
- In vitro cellular assays were performed to evaluate the direct anti-tumor effects of the NBs.
- In vivo mouse immunization models were used to assess the systemic immune responses and anti-tumor efficacy.
Main Results:
- Ce6@aPD-L1 NBs effectively generated reactive oxygen species, leading to tumor cell death.
- In vivo studies showed enhanced immune responses, including immunogenic cell death and activation of dendritic cells and CD8+ T cells.
- The nanobubbles demonstrated significant anti-tumor activity in mouse models.
Conclusions:
- Ce6@aPD-L1 NBs facilitate targeted delivery of therapeutic agents to the tumor site.
- These NBs activate anti-tumor immunity and sonodynamic therapy, offering a dual-action approach.
- Ce6@aPD-L1 NBs hold substantial potential for synergistic anti-cancer effects in prostate cancer.
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