# Mitigating Long-term Cardiotoxicity with Nanoparticle Encapsulated Anthracyclines

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2021 · $218,685

## Abstract

Survivors of pediatric cancers disproportionately experience subsequent cardiovascular disease. Pediatric
cancer survivors are seven times more likely to die of cardiovascular disease compared to the general
population. Commonly used anthracycline chemotherapeutic agents, particularly doxorubicin, have been
implicated in late cardiovascular disease in cancer survivors, with cumulative dose being the most important
risk factor. Studies have shown that even at lower doses of anthracycline exposure (under 100mg/m2), 30% of
patients’ hearts show signs of structural abnormalities 6 to 20 years after diagnosis. Strategies to reduce
anthracycline-induced cardiotoxicity, including continuous infusion of liposomal doxorubicin or administration of
dexrazoxane have not been approved for pediatric use and are not widely adopted in this patient population.
 This project seeks to advance the development of a patented Apo-A1 mimetic peptide / fatty acid conjugate
that self-assembles into micellar structures termed Myr5A-nanoparticles (Myr5A NPs). Myr5A NPs can
encapsulate and deliver therapeutic payloads to cancer cells. The synthetic Apo-A1 mimetic peptide
component, like Apo-A1 found in physiologic HDL, functionally engages the scavenger receptor class B type 1
(SR-B1) cell surface receptor, resulting in the transfer Myr5A NP drug payloads into the target cell through
selective uptake. The selective uptake process is not endosomally-mediated, resulting in delivery of Myr5A NP
payloads directly to the cytoplasm. In addition, highly hydrophobic payloads may be efficiently delivered.
Myr5A NPs have exhibited long circulating half-lives in animal studies and would be inexpensive to produce at
commercial scale. Previous studies have demonstrated SR-B1 expression in a range of tumor cells, in addition
to hepatocytes, steroidogenic tissues, and macrophages. The Yustein Lab at Texas Children’s Hospital has
confirmed expression of SR-B1 in Ewing sarcoma and other pediatric sarcomas.
 Based on these observations, we hypothesize that agents encapsulated in Myr5A NPs will selectively target
Ewing sarcoma cells with high expression of SR-B1 and spare normal tissues with low SR-B1 expression, such
as the heart and kidneys. To test this hypothesis, the Aune Lab will work collaboratively with the Yustein Lab at
Texas Children’s Hospital and Qana Therapeutics to evaluate the expression of key DNA damage markers
induced by Myr5A NPs loaded with novel anthracyclines (AD198 and valrubicin) in EWS cell lines and cardiac
cells in vitro. In addition, we will simultaneously evaluate the antitumor efficacy and cardiac toxicity profile of
these agents in vivo, using a unique model developed by the Aune lab to study anthracycline-induced
cardiotoxicity. This project will facilitate collection of critical preclinical data by this collaborative group that will
lay the foundation for a collaborative clinical trial supported by academia, industry and advocacy groups.
Further clinical devel...

## Key facts

- **NIH application ID:** 10195941
- **Project number:** 1R21HL157810-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** GREGORY J. AUNE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $218,685
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195941

## Citation

> US National Institutes of Health, RePORTER application 10195941, Mitigating Long-term Cardiotoxicity with Nanoparticle Encapsulated Anthracyclines (1R21HL157810-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10195941. Licensed CC0.

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