Investigation of Advanced Cavitation Agents for Nanoparticle-Mediated Histotripsy (NMH) Applications

Nanoparticle-mediated histotripsy (NMH) is an emergent non-invasive therapy that uses nanoparticles in combination with focused ultrasound with engineered nanoparticles to mechanically ablate targeted tissue with cavitation. Unlike conventional histotripsy, which requires high negative pressures (>25 MPa) for treatment, NMH utilizes nanoparticles, which enable cavitation at significantly lower pressures (<15 MPa), and, thus, improves the safety and precision of the therapy. Due to the increased safety profile of NMH, potential applications across a broader range of tissue types and anatomical sites are possible. As a versatile and tunable platform, NMH offers the ability to integrate dual-function nanoparticles that enable mechanical ablation with localized drug delivery, all within a single treatment modality. To date, NMH has demonstrated proof-of-concept success in applications such as prostate cancer ablation and catheter-based biofilm removal. However, its full potential as a multifunctional therapeutic platform for more complex disease environments remains underexplored. In this dissertation, I investigate the feasibility and optimization of NMH for two clinically relevant and challenging scenarios: the treatment of breast cancer and the eradication of biomaterial-associated infections. Specifically, this work focuses on: (1) the characterization of NMH cavitation agents with clinically relevant pulsing parameters, (2) the feasibility of NMH as a breast cancer treatment, and (3) the characterization and feasibility of dual-function NMH cavitation agents for the treatment of breast cancer and biomaterial-associated infections. Through this research, I demonstrate how NMH can be strategically tuned to meet the demands of different clinical presentations by strategically using nanoparticles. This work will establish NMH as a flexible, precise, and multi-functional treatment platform. Ultimately, this dissertation contributes to the development of a next-generation therapeutic approach that bridges the gap between mechanical ablation and drug delivery, all enabled through nanoparticle-mediated cavitation.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biomedical Engineering

Department dc:contributor.department

Department of Biomedical Engineering and Mechanics

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2025

Author dc:creator

• Hall, Sarah Louella

Chair dc:contributor.committeechair

• Vlaisavljevich, Eli

Committee members dc:contributor.committeemember

• Allen, Irving C.
• Sheybani, Natasha
• Durmaz, Yasemin
• Munson, Jennifer M.

• nanoparticle
• focused ultrasound
• histotripsy
• breast cancer
• biofilms

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

vt_gsexam:43562

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/134310