# Ultrasound-triggered red blood cell drug delivery with photoacoustic tracking

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $571,437

## Abstract

Our overarching goal is to develop a dual photoacoustic-ultrasound guided drug delivery for cancer.
Improvement of therapeutic delivery to solid tumors is urgently needed to address toxicity of the systemic dosing of
cancer drugs. Development of efficient delivery methods has been slow; overall long-term survival gains of cancer
patients over the past decades are very modest.
 We propose a fluorocarbon-particle-modified red blood cell (RBC) as acoustically active drug carrier.
These natural particles offer excellent drug loading capacity, and can be easily used for site-specific targeting, by
decorating them with ligands towards tumor vasculature biomarkers or magnetic particles. Decorating RBCs with
perfluorocarbon nanodroplets allows rapid rupture of RBC membrane in response to a single short ultrasound
pulse, resulting in rapid (<1 sec) payload release. By combining these carriers with ultrasound and photoacoustic
imaging or SPECT, we expect that ultrasound-controlled release of encapsulated drugs, guided by imaging, will
bring significant antitumor effects. We have demonstrated ultrasound-mediated RBC rupture and dye release of
entrapped in vitro. We will then encapsulate in aaRBCs a chemotherapeutic doxorubicin and immunotherapeutic
imiquimod (currently used topically) and demonstrate delivery in an in vivo murine tumor model.
 Aim 1. Elucidate ultrasound triggered release mechanism of red blood cell carriers. Acoustically active
red blood cells (aaRBCs) are made by attaching perfluorocarbon nanodroplets (NDs) to the RBC membrane. Drug
release is triggered by acoustic activation, causing the NDs to vaporize into micron-size microbubbles and rupture
the RBC membrane. Our high-speed camera, used to capture ultra-fast dynamics of droplets and microbubbles,
will be used to image vaporization of droplets attached to RBC membranes. Optimal aaRBC and ultrasound
design parameters that trigger release of >50% of encapsulated drug will be determined in vitro.
 Aim 2. Achieve targeting and imaging functionality of long-circulating aaRBCs. aaRBC molecular
targeting to the vascular endothelium will be achieved through conjugation of a cyclic Arg-Gly-Asp (RGD) peptide
and vascular endothelial growth factor (scVEGF) to the RBC membrane. Magnetic targeting will be achieved by
loading magnetic nanoparticles. Radiolabeled aaRBCs will be used to assess biodistribution of targeted aaRBCs
in a murine tumor model, augmented with SPECT imaging. An approved NIR dye, indocyanine green (ICG), will be
encapsulated into RBCs and imaged using a photoacoustic system, for real-time release control.
 Aim 3. Demonstrate image-guided therapy in a mouse tumor model with aaRBCs and ultrasound. We
will use a targeted aaRBC loaded with doxorubicin and/or imiquimod, along with ICG dye. We will trigger release
and monitor delivery using a photoacoustic/ultrasound and SPECT. Therapy will be performed in a mouse
hindlimb MC38 colon adenocarcinoma; delay of tumor growth assessed post...

## Key facts

- **NIH application ID:** 9858330
- **Project number:** 5R01EB023055-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** ALEXANDER L KLIBANOV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $571,437
- **Award type:** 5
- **Project period:** 2017-05-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858330

## Citation

> US National Institutes of Health, RePORTER application 9858330, Ultrasound-triggered red blood cell drug delivery with photoacoustic tracking (5R01EB023055-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858330. Licensed CC0.

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