Bubble cloud-mediated cavitation for tumor mechanical ablation and effector immune cell deployment

Area of Science:

• Biomedical Engineering
• Acoustic Medicine
• Cancer Therapy

Background:

• Histotripsy is a non-invasive tumor ablation technique utilizing ultrasound-induced cavitation.
• Optimizing cavitation behavior is crucial for precise histotripsy and effective tumor destruction.
• Perfluoropentane (PFP)-loaded nanodroplets can serve as exogenous nuclei to enhance cavitation generation.

Purpose of the Study:

• To investigate the cavitation behavior of bubble clouds generated by PFP-loaded nanodroplets under varying ultrasound intensities.
• To evaluate the efficacy of nanodroplet-activated bubble cloud cavitation in tumor ablation.
• To determine the impact of different cavitation patterns on anti-tumor immune responses.

Main Methods:

• PFP-loaded nanodroplets (approximately 200 nm) were used as cavitation nuclei.
• Bubble cloud formation, vibration, and collapse were studied in solution and phantom models.
• Ultrasound intensities were varied to observe distinct cavitation patterns.
• Immunogenic cell death (ICD) induction and immune cell infiltration (including CD8+ T cells) were assessed at cellular and animal levels.

Main Results:

• Two distinct cavitation patterns were observed: continuous vibration from slow nanodroplet vaporization and rapid collapse from fast vaporization.
• Both patterns induced immunogenic cell death (ICD), releasing damage-associated molecular patterns (DAMPs).
• Ultrasound intensity of 0.5 W/cm² resulted in the highest CD8+ T cell infiltration in the tumor core.
• Sustained bubble cloud oscillation demonstrated superior enhancement of effector immune cell infiltration compared to rapid collapse.

Conclusions:

• Sustained bubble cloud oscillation, achieved through controlled nanodroplet vaporization, is more advantageous for antitumor therapy than rapid bubble collapse.
• This approach effectively induces ICD and promotes significant infiltration of effector immune cells, particularly CD8+ T cells.
• Histotripsy utilizing PFP-loaded nanodroplets offers a promising strategy for enhancing anti-tumor immunity and therapeutic outcomes.