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Nanoparticle-mediated Histotripsy (NMH) for Noninvasive and Targeted Ablation of Metastatic Breast Cancer

Award Number: R21EB027979
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Breast cancer is the most common malignancy among women, with almost 1.7 million patients diagnosed annually. Although promising treatment options are currently available, metastatic disease remains a significant challenge. Indeed, the vast majority of breast cancer deaths are a direct consequence of metastasis and no cure is available once metastatic disease has developed. Thus, new treatment strategies are needed to eliminate mortality associated with metastatic breast cancer. This proposal is focused on the development of nanoparticle-mediated histotripsy (NMH) as a non-invasive and targeted ablation method for the treatment of multi-focal breast tumors. Histotripsy is a non-invasive, non-ionizing, and non-thermal ultrasound ablation method that destroys tissue through the precise control of acoustic cavitation generated by high- pressure (>25-30 MPa) pulses. Histotripsy does not have the limitations of thermal ablation and can produce consistent ablation, even in near vessels. Additional benefits of histotripsy include high precision and real-time imaging guidance. However, although histotripsy shows promise as an improved ablation method for the treatment of primary tumors, this treatment method requires high ultrasound pressures and remains limited to tumors that can be identified and imaged prior to treatment, which is often not feasible in metastatic breast cancer patients with multiple tumor nodules. To address this need, our team recently invented NMH as a targeted ablation approach for treating multi-focal tumors by combining perfluorohexane (PFH) nanoparticles with histotripsy. NMH takes advantage of the significantly reduced cavitation threshold of these particles, allowing for histotripsy to be selectively generated only in regions containing the particles. In this proposal, we develop NMH for the selective ablation of metastatic breast tumors. In Aim 1 we engineer and characterize PFH “nanocones” with a smaller size (~50nm), higher stability, and functionalized targeting capabilities compared to our previously tested particles. Aim 2 will test the in vitro feasibility of these PFH “nanocones” for targeting and selectively ablating breast cancer cells in a tissue engineered 3D breast cancer model. Aim 3 will investigate the in vivo feasibility of NMH for the targeted ablation of metastatic breast tumors in an orthotopic mouse model. Together, these studies are expected to demonstrate the feasibility of NMH for multi-focal tumor ablation, which is essential to establishing the potential of this new technology. If successful, this work will lay the foundation for NMH as a targeted multi-focal cancer therapy capable of significantly improving the standard of care for cancer patients by increasing targeting specificity and treating tumors too small to detect by imaging.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$44,584 )
2023	2022	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	9/7/2023	NON-COMPETING CONTINUATION	-$44,584
														Subtotal = -$44,584

Issue Date FY: 2022 ( Subtotal = $184,698 )
2022	2022	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	8/2/2022	NON-COMPETING CONTINUATION	$18,470
2022	2022	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	11/9/2021	NON-COMPETING CONTINUATION	$166,228
														Subtotal = $184,698

Issue Date FY: 2021 ( Subtotal = $227,518 )
2021	2021	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	3/20/2021	NON-COMPETING CONTINUATION	$227,518
2021	2021	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	5/26/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $227,518

Issue Date FY: 2020 ( Subtotal = $190,371 )
2020	2020	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	2/7/2020	NEW	$190,371
														Subtotal = $190,371

Grand Total All Awards = $558,003

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Nanoparticle-mediated Histotripsy (NMH) for Noninvasive and Targeted Ablation of Metastatic Breast Cancer

Award Number: R21EB027979

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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