# Enhancement of tumor radiation response by ultrasound-driven nanobubble stimulation

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $497,377

## Abstract

Project Summary
Radiation is a mainstay of cancer treatment, yet challenges remain. The long term goal of the proposed research is to
transform traditional cancer radiation therapy protocols by including a pre-treatment step involving perturbing the vascular
and cellular function of tumors with ultrasound-activated radiosensitizing nanobubbles (NBs). The new paradigm in cancer
treatment protocol builds upon a decade of prior work that used commercial microbubbles (MBs) to elicit a radiosensitizing
effect. The MB radiosensitization effects are primarily intravascular, with significant endothelial damage incurred. In
contrast, in the strategy proposed here, we hypothesize that the NBs will also extravasate into the tumor parenchyma, which
will result in significant increases in direct damage to the cancer cells, in addition to the vascular damage. Thus the effect
will be both intra- and extra-vascular. The tumors treated in this way will respond better to radiation, lowering the effective
radiation dose and decreasing residual surviving tumor. The technique further allows targeting of tumor specific volumes
allowing healthy tissues to be spared. We have demonstrated in preliminary studies in vivo that ultrasound-activated NB
perturbation of tumors results in a significantly greater enhancement in tumor kill compared to MBs when followed by
traditional radiation therapy.
This approach could markedly improve existing therapies and reduce the associated side-effects. This is clinically important
for prostate cancer treatment where collateral damage and off-target effects are common and lead to years of complications
in many patients. Therefore, we propose a set of four specific aims to test, develop, optimize, demonstrate and quantify the
efficacy of this novel technique in prostate cancer. Aim 1 will focus on the development of stable, uniformly-sized
radiosensitizing NBs. The acoustic and bio-activity of the bubbles will be measured, and baseline biodistribution in tumor
bearing mice will be carried out. In Aim 2, the NBs will be tested in combination with radiation in a mouse model of prostate
cancer so that treatment parameters can be optimized. In Aim 3, carried out concurrently with Aim 2, we will develop a
photoacoustic imaging approach for monitoring early treatment response. This tool will be used to predict therapeutic
efficacy and completeness of tumor treatment as soon as 2 hours after the therapy. Finally, in Aim 4, we will test the
combination approach in a large (rabbit) orthotopic model of human prostate cancer.
We have assembled a multidisciplinary MPI team of investigators with a demonstrated track record of collaborative work
in this field. The team includes Dr. Czarnota MD/Ph.D., a physician-scientist and discoverer of the original MB sensitizing
approach now in clinical trials, Dr. Michael Kolios Ph.D. is a medical physicist with broad experience in photoacoustic
imaging for therapy response and ultrasound physics and Dr. Agata Ex...

## Key facts

- **NIH application ID:** 10316459
- **Project number:** 1R01CA260826-01A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Gregory Jan Czarnota
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $497,377
- **Award type:** 1
- **Project period:** 2021-08-11 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316459

## Citation

> US National Institutes of Health, RePORTER application 10316459, Enhancement of tumor radiation response by ultrasound-driven nanobubble stimulation (1R01CA260826-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10316459. Licensed CC0.

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