# Therapeutic nanoscale matrimeres

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $438,765

## Abstract

PROJECT SUMMARY
The extracellular matrix in tissue is significantly disrupted in many disease conditions, but it is essential for
cells to function. Endothelial cells become leaky when they no longer receive functional matrix signals upon
tissue injury. Failure to restore endothelial barrier function can result in persistent edema, long-term tissue
damage, and irreversible tissue fibrosis. Since many organs are highly vascularized, there is a need to find a
general solution to treat tissue injury by restoring matrix-mediated signaling. There is currently no effective
strategy to achieve this goal, since the activation of matrix signaling pathways requires the delivery of matrix
molecules with proper molecular conformation and physiochemical properties. Here, we define a novel class of
cell-secreted, non-vesicular nanoparticles that bear matrix molecules, which we call matrimeres. Our
preliminary data show that mesenchymal stromal cells naturally secrete matrimeres consisting of fibronectin
and DNA, which can directly activate endothelial cells to restore junctions disrupted by endotoxemia-induced
injury. Importantly, we show that functional matrimeres can be reconstituted from purified fibronectin protein
and genomic DNA fragments in a chemical environment similar to secretory compartments in cells. We will
build on these results to test the hypothesis that fibronectin matrimeres treat tissue injury by restoring
endothelial barrier function. In Aim 1, we will determine how fibronectin matrimeres restore endothelial barrier
function after inflammatory injury in the lungs. In Aim 2, we will investigate biogenesis mechanisms of
fibronectin matrimeres in mesenchymal stromal cells. In Aim 3, we will engineer synthetic matrimeres that
restore endothelial barrier function. We predict that highly functional nanomedicine can be developed based on
the fundamental insight that cells are able to recycle and repackage matrix molecules into nanoparticles by
complexing with DNA fragments, which circulate in the body and play a homeostatic role in limiting vascular
permeability. The project is highly multidisciplinary in that it will employ a combination of expertise in nanoscale
biology, nanotechnology, chemical, biomaterials, computational, advanced imaging, cellular and molecular
biology, and in vivo approaches to address the specific aims. The results will help develop a number of
fundamental concepts of matrimeres in terms of their mechanisms of action, biogenesis, and reverse
engineering. Success of the project will also enable the generalization of matrimeres as natural nanomedicine
to deliver macromolecules for improved regenerative outcomes.

## Key facts

- **NIH application ID:** 10806215
- **Project number:** 5R01EB034507-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Jae-Won Shin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $438,765
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806215

## Citation

> US National Institutes of Health, RePORTER application 10806215, Therapeutic nanoscale matrimeres (5R01EB034507-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10806215. Licensed CC0.

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