# A novel approach to delivering therapeutics in heart transplantation

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $692,505

## Abstract

Abstract
 Cardiac transplantation has become a life-saving strategy for patients with irreversible heart disease.
While the development of immunomodulatory drugs (IMD) has played a pivotal role in the success of heart
transplantation, nonetheless, there is a substantial unmet need to improve the long-term outcomes of heart
transplantation. A large number of cardiac transplant recipients lose their heart transplants due to chronic
microvascular injuries. Furthermore, they are also at substantial risk for losing their native organs (such as the
kidneys) due to the microvascular toxicities. IMD contribute both directly to these microvascular toxicities by
mediating endothelial injuries, and indirectly by playing a pathogenic role in the development of diabetes, the
metabolic syndrome and hypertension post-cardiac transplantation. Other serious side effects of IMD include
systemic infection and post-transplant malignancy. Therefore, there is a significant unmet need for the
development of novel strategies which increase the efficacy and reduce the toxicity of IMD. This proposal
seeks to establish an innovative nanodelivery system of IMD in heart transplantation. Pursuing our preliminary
data, we will test the hypothesis that targeted delivery of IMD to the draining lymph nodes (DLN) and heart
allografts increases the efficacy of IMD, thereby significantly reducing their systemic dosing. The latter should
result in reduced systemic toxicity as well. The scientific premise of this proposal is soundly supported by the
wealth of information demonstrating that lymphoid tissue are the critical loci for the formation of alloreactive T
cells, which eventually home to cardiac allografts and cause cardiac rejection. The field of nanotechnology
has created unprecedented opportunities to lay the groundwork for transformative approaches to change the
landscape of drug delivery. However, the application of nanomedicine to heart transplantation remains to be
developed. Over the past several years, we have developed the first class of nanocarriers for the delivery of
IMD to DLN and heart transplants with significant clinical efficacy. These data significantly support the
feasibility of the proposed studies. In Aim 1, we plan to characterize and further improve the delivery of IMD
to the DLN to further promote heart allograft survival. The proposed studies will employ murine heart transplant
models, established functional assays and sophisticated imaging studies to better understand the
biodistribution of IMD and their nanocarriers. In Aim 2, we will study the underlying mechanisms by which
delivering IMD to the DLN controls the balance of alloreactive T cells and regulatory T cells. In Aim 3, we will
capitalize on the unique setting of transplantation where we can deliver IMD directly to heart organs prior to
transplantation. These innovative and clinically feasible approaches enable for the first-time better control of
the organ’s inflammatory milieu which signific...

## Key facts

- **NIH application ID:** 10001633
- **Project number:** 5R01HL145813-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Reza Abdi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $692,505
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001633

## Citation

> US National Institutes of Health, RePORTER application 10001633, A novel approach to delivering therapeutics in heart transplantation (5R01HL145813-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001633. Licensed CC0.

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