# Macrophage-Mediated Delivery of Acoustically Propelled Nanoparticles for Sensitizing Immunologically Cold Tumors

> **NIH NIH R21** · UNIVERSITY OF COLORADO · 2022 · $174,300

## Abstract

ABSTRACT
The overall goal of this project is to simultaneously reprogram immunologically cold tumors and destroy tumor
cells through the targeted delivery of cavitation-enhancing nanoparticles by adoptive macrophage transfers.
Engineered immune cells have the capacity to treat patients with relapsing or refractory cancers. However,
antigen-directed therapies like CAR T-cell therapy have shown limited efficacy in some advanced cancers due
to the highly immunosuppressive microenvironment of solid tumors, expression of immune checkpoints, and lack
of tumor-associated antigens. Thus, there is a need for therapies that are agnostic to the expression of tumor-
associated antigens and that sensitize solid tumors to established antigen-directed therapies. To meet this
important need, we will develop an adoptive cellular transfer technology to deliver a class of propulsive
nanoparticles to solid tumors. Delivery of nanoparticles inside of macrophages will increase their accumulation
within tumors and reduce off-target toxicity. Once localized, the highly porous design of the silica nanoparticles
promotes the nucleation and growth of bubbles on their surfaces to guide their rapid and efficient penetration
through dense tumorous tissue in response to high-intensity focused ultrasound (HIFU). By loading
immunomodulatory drugs that stimulate macrophages into the nanoparticles, we will simultaneously lyse cancer
cells and repolarize a large volume of neighboring tumor-associated macrophages (TAMs) toward antitumor
phenotypes, providing amplified stimulation of the tumor immune microenvironment. The unique combination of
particle propulsion and enhanced transport of drugs will maximize the repolarization of TAMs and eventually
other immune cells by the inclusion of different drugs. In this R21 project, our primary goals are to validate the
biodistribution, propulsion, and immunomodulatory effects of the nanoparticles in murine 4T1 mammary
carcinoma models, which will allow us to later study the capabilities of this technology in other aggressive tumor
models. The outcome of this work will be an adoptive cell transfer technology to deliver propulsive nanoparticles
for treating solid tumors that are weakly immunogenic in a way that is extendable to a variety of cancers.
Feasibility for this work is supported by the expertise of the PIs: nanoscale interfacial engineering (Goodwin) and
adoptive macrophage transfers to solid tumors (Shields) for a multipronged approach to stimulate TAMs and
eventually other tumor-associated immune cells. We will develop this technology through the following Specific
Aims: 1) Design particles for cavitation-based drug release in macrophages. 2) Understand effects of focused
ultrasound on acoustically triggered nanoparticles on tumor spheroid models. And 3) Evaluate the therapeutic
potential of macrophage-mediated transport of particles to tumors after ultrasound stimulation.

## Key facts

- **NIH application ID:** 10512775
- **Project number:** 1R21CA267608-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Andrew P Goodwin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $174,300
- **Award type:** 1
- **Project period:** 2022-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10512775

## Citation

> US National Institutes of Health, RePORTER application 10512775, Macrophage-Mediated Delivery of Acoustically Propelled Nanoparticles for Sensitizing Immunologically Cold Tumors (1R21CA267608-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10512775. Licensed CC0.

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