# Adipose-derived biogenic nanoparticles for treatment of myocarditis/DCM(MPDPI)

> **NIH NIH R21** · MAYO CLINIC  JACKSONVILLE · 2021 · $195,625

## Abstract

PROJECT SUMMARY
Myocarditis caused by viral infections is a leading cause of sudden death and can progress to dilated
cardiomyopathy (DCM) and the need for a heart transplant. Currently, there are no disease-specific therapies
to reduce myocarditis or prevent progression to DCM. Toll like receptor 4 (TLR4) is known to promote viral
myocarditis, triggering proinflammatory cascades that promote acute heart failure and progression to DCM.
Thus, there is a need to develop novel therapies that suppress TLR4-driven inflammation to ameliorate
myocarditis. Recent studies have indicated that adipose-derived stem cells (ADSCs) have anti-inflammatory
effects that are mediated by cell-secreted biogenic nanoparticles (BiNPs). However, the immunomodulatory
properties of heterogeneous adipose tissue-derived BiNPs have not been explored. Our preliminary results
indicate that adipose tissue-derived BiNPs: (i) suppress TLR4-induced inflammatory responses in
macrophages, (ii) reduce inflammation and TLR4 expression in a mouse model of viral myocarditis, (iii) take
less time to process, cost less to obtain, and are more abundant compared to cell culture-derived BiNPs, and
(iv) can be loaded with conventional drugs that further enhance anti-inflammatory effects. We hypothesize that
adipose-derived BiNPs reduce TLR4-induced activation of inflammation in the heart and can be used to treat
myocarditis and DCM. To test this hypothesis, we will determine the mechanism of patient-derived lipoaspirate-
derived BiNPs (Lipo-NPs) in a mouse model of myocarditis/ DCM (Aim 1), and assess the performance of
patient-derived Lipo-NPs as drug delivery vehicles for anti-inflammatory compounds in a mouse model of
myocarditis (Aim 2), measuring the biodistribution of Lipo-NPs in healthy and male and female mice with
myocarditis and determining the effect of Lipo-NPs loaded with anti-inflammatory agents on myocarditis by
sex. We will utilize our laboratory's expertise in BiNP isolation along with a well-characterized murine viral
myocarditis/ DCM model. We anticipate that this study will delineate the role of adipose BiNPs in myocarditis/
DCM and potentially lead to new clinically relevant therapeutic strategies.

## Key facts

- **NIH application ID:** 10089412
- **Project number:** 5R21AI152318-02
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** DeLisa Fairweather
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $195,625
- **Award type:** 5
- **Project period:** 2020-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089412

## Citation

> US National Institutes of Health, RePORTER application 10089412, Adipose-derived biogenic nanoparticles for treatment of myocarditis/DCM(MPDPI) (5R21AI152318-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10089412. Licensed CC0.

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