# Development of Novel Acoustic Clusters for Improving Combinatorial Neuroblastoma Therapy

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2020 · $357,124

## Abstract

Development of Novel Acoustic Clusters for Improving Combinatorial Neuroblastoma Therapy
Summary: The goal of this project is to develop superior image-guided methods of delivering
chemotherapeutics to neuroblastoma, which are aggressive solid tumors responsible for 15% of childhood
cancer related mortalities. Neuroblastoma most commonly arises in the adrenal gland and kidneys, but also
other areas of the abdomen. Unlike many tumors, neuroblastomas are poorly perfused, requiring high-dosage
chemotherapy, which can have deleterious short and long-term side effects in children. Currently, no clinical
methods exist to optimize drug uptake in neuroblastoma in vivo. Methods of improving drug delivery to tumors
are needed to improve therapy.
In this study, we propose an innovative image-guided combinatorial drug therapy approach to remodel the
tumor vasculature and treat neuroblastoma, using anti-VEGF antibody, bevacizumab (BV), in combination with
acoustically delivered liposomal doxorubicin (L-DOX). Neither BV therapy nor L-DOX are currently indicated for
neuroblastoma treatment, but together with sound-sensitive ultrasound contrast agents (UCA's) they have the
potential to dramatically improve neuroblastoma treatment efficacy. BV therapy was designed to induce
vascular regression, however we and others have demonstrated that repetitive BV therapy causes vascular
remodeling in NGP mouse tumor models by “cooption” of surrounding vessels and potentially making them
more amenable to drug uptake by reducing mature pericyte coverage thereby compromising vascular integrity.
In combination with BV therapy, we will test a novel platform for enhancing drug uptake in tumors utilizing
ultrasound sensitive particles, called “Acoustic Clusters” (ACs), to maximize payload of doxorubicin specifically
to tumor tissue. ACs are chemically crosslinked gas-filled spheres (“microbubbles”, ~1 μm diameter each) that
vibrate in an ultrasound field. AC's are assembled using drug carrying liposomes and are specifically designed
to solubilize liposome-encapsulated drugs on-demand during ultrasound stimulation. ACs can also
permeabilize blood vessels facilitating uptake of released drugs. We will test several novel image-guided drug
delivery strategies using microbubble (and nanodroplet) based ACs to “uncage” encapsulated doxorubicin
(with and without permeabilizing blood vessels) to maximize drug uptake in tumors. The strategy of
simultaneously releasing drugs and permeabilizing vasculature is a novel approach that will enable more
efficient drug targeting and eliminate the reliance on endogenous tumor vascular permeability for liposome
encapsulated drug carrying molecules, such as L-DOX. The techniques developed in this study would be
applicable to a wide range of drugs and cancers toward improving overall treatment efficacies.

## Key facts

- **NIH application ID:** 9891989
- **Project number:** 5R01CA235756-02
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Sonia Lorena Hernandez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,124
- **Award type:** 5
- **Project period:** 2019-03-12 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891989

## Citation

> US National Institutes of Health, RePORTER application 9891989, Development of Novel Acoustic Clusters for Improving Combinatorial Neuroblastoma Therapy (5R01CA235756-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891989. Licensed CC0.

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