# Nanoparticle-mediated reprogramming of circulating monocytes and neutrophils to decrease inflammation-mediated damage after trauma

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $672,096

## Abstract

Summary: Regeneration of tissues following injury can be limited due to the development of strong inflammatory
responses that can lead to substantial cell death and inappropriate conditioning of the local environment, which
becomes deficient in stimulatory factors and has an excess of inhibitory factors. Our long-term goal is to develop
nanoparticles that reprogram the phenotype of monocytes and neutrophils in the blood after trauma, resulting in
altered trafficking and anti-inflammatory phenotypes that reduce the extent of damage and may support an
environment that leads to enhanced regeneration. The premise of the proposed research is based on our
preliminary data indicating the ability to deliver nanoparticles in a minimally invasive manner that target
inflammatory monocytes and neutrophils in the blood to reprogram their function, which leads to substantial
functional recovery in a spinal cord model. The particles may enhance recovery by multiple mechanisms,
including reducing immune cell accumulation at the injury, modulating the splenic microenvironment that is
known to coordinate inflammatory responses, or directly inducing an anti-inflammatory or pro-regenerative
environment at the injury. The following aims employ nanoparticles with differential binding to monocytes and
neutrophils, which influences their phenotype such as trafficking and cytokine production. Importantly, the
reprogramming is mediated solely by the physicochemical properties of the nanoparticles (e.g., size, charge,
composition) and does not involve an active pharmaceutical ingredient (API), which have been discontinued
from many applications due to the risk-benefit ratio. The focus herein is to identify the mechanism by which the
particles are enhancing functional recovery, which may also identify design parameters that are more efficient.
Aim 1 will investigate nanoparticle association with innate immune cells in circulation, and their subsequent
trafficking and phenotype in the inflammatory response. Nanoparticle injection following SCI has led to
substantial recovery gains we aim to identify the mechanisms by which the particles are promoting recovery.
Particles that induce differential binding, phenotypic polarization, and trafficking of monocytes and neutrophils
will be investigated. Aim 2 will investigate the impact of the reprogrammed immune cells on the microenvironment
within the spleen and spinal cord. Stromal and immune cells are initially investigated throughout recovery, and
we subsequently investigate the extent of axon growth, myelination, and functional recovery. Collectively, these
studies will determine the relationship between nanoparticle properties, immune modulation, and the capacity of
the environment to reduce damage and enhance functional recovery. We propose that the particles that
reprogram based on their physicochemical properties have the potential to be a transformational therapy for
trauma by providing a readily available, non-invasive mea...

## Key facts

- **NIH application ID:** 10437650
- **Project number:** 5R01AI148076-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Aileen J Anderson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $672,096
- **Award type:** 5
- **Project period:** 2019-07-16 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437650

## Citation

> US National Institutes of Health, RePORTER application 10437650, Nanoparticle-mediated reprogramming of circulating monocytes and neutrophils to decrease inflammation-mediated damage after trauma (5R01AI148076-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10437650. Licensed CC0.

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