# Immune-modifying nanoparticles for the treatment of traumatic brain injury

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $424,294

## Abstract

Traumatic Brain Injury (TBI) is a major health issue. After the primary injury, there is substantial secondary injury
attributable to infiltrating immune cells, cytokine release, reactive oxygen species, excitotoxicity, and other
mechanisms. Despite many preclinical and clinical trials designed to limit such secondary damage, no successful
therapies have emerged. However, we have found that Immune-modifying nanoParticles (IMP) are a strong
candidate for a clinically translatable acute pharmacologic intervention for TBI. IMP are highly negatively
charged, 500 nm-diameter particles composed of the FDA-approved biodegradable biopolymer, carboxylated
poly(lactic-co-glycolic) acid (PLGA-COOH). After intravenous (IV) administration, IMP bind to the macrophage
receptor with collagenous structure (MARCO) on monocytes. Monocytes bound to IMP no longer travel to sites
of inflammation, but instead are sequestered in the spleen. Because IMP specifically target the MARCO+ subset
of monocytes, it is distinctly different from other approaches that non-specifically target all monocyte/macrophage
lineage cells including microglia. IV treatment with IMP in two different TBI models profoundly reduced the
number of immune cells infiltrating into the brain, mitigated the inflammatory status of the infiltrating cells, and
reduced levels of an array of cytokines and chemokines. More importantly, IMP treatment resulted in attenuated
edema, preservation of brain tissue, and significant preservation of both physiologic visual and motor function.
The proposed studies will examine IMP-mediated changes in gene expression that alter the inflammatory status
of infiltrating cells, limit gliosis, reduce edema, and promote neuronal survival. They also will examine effects of
IMP on other cell types including microglia, progenitor cells, and other immune cells. Notably, IMP are made of
an FDA-approved material that is stable at room temperature and could easily be given immediately IV after TBI
in the field by EMTs or in the emergency room. Mechanistically the proposed studies will help to understand
more clearly the effects of infiltrating hematogenous monocyte-derived macrophages after TBI. Significantly,
they also will help to develop a potentially effective and practical therapy for human TBI.

## Key facts

- **NIH application ID:** 10404562
- **Project number:** 5R01NS117476-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JOHN A KESSLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $424,294
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404562

## Citation

> US National Institutes of Health, RePORTER application 10404562, Immune-modifying nanoparticles for the treatment of traumatic brain injury (5R01NS117476-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10404562. Licensed CC0.

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