# Multiscale considerations for immune engineering at mucosal interfaces

> **NIH NIH R35** · UNIVERSITY OF DELAWARE · 2021 · $400,000

## Abstract

Project Summary
 The long-term goal of the Fromen lab is to develop personalized immunomodulatory mucosal therapeutics
using particle immune engineering. Mucosal surfaces line the respiratory, gastrointestinal, and urogenital tracts
and serve as the first barrier to foreign invasions. These interfaces are home to the mucosal immune system, a
specialized arm of the host immune protection that maintains balance at these critical barriers. Dedicated cells
at the mucosa regulate commensal bacteria and maintain tolerance, while also mounting responses to combat
pathogenic infections. In the past two decades, engineered particle platforms have emerged as a convenient
way to interact with innate immune cells, providing precise chemical cues and pathogen mimicry capable of
instructing immune response. Despite the overwhelming potential to directly regulate mucosal immune function
at these essential interfaces, most advances to date in particle-inspired immune engineering have bypassed the
mucosal interface altogether and instead focused on parenteral routes of administration. There is a critical need
to develop particle immune engineering approaches that are designed specifically for the mucosal environment,
that can overcome the unique multiscale obstacles faced in mucosal drug delivery. Broadly, there are two major
challenges of particle-driven immune engineering at mucosal interfaces that must be addressed to generate
needed translational advances: 1) overcoming the dynamic barrier function of the mucosal immune system and
2) tailoring effective stimulatory cues specifically to mucosal antigen presenting cells (APCs) for desirable
responses. The Fromen lab has focused our short-term goals on generating fundamental advances in these two
challenge areas, specifically using the respiratory tract as a model mucosal system. Major advances to date
have included evaluation of novel nanoparticle platforms within the respiratory tract for lung APC modulation,
discovery of particle-driven regulation over APC lifespan, and creation of full-size respiratory model systems. In
this proposal, we will continue our efforts to engineer personalized immunomodulatory mucosal therapeutics.
We will continue to develop tools at the chemical-biology interface that control cellular-APC interactions and
subsequent cellular and microenvironment response. We will simultaneously advance macroscopic transport
models to bridge the gap between organ-level and mucosal microenvironment motion that will advance multiple
physiological applications. These future efforts are well suited to the research program, given the widely
applicable multiscale experimental framework to address the broad challenges presented by the dynamic
mucosal interfaces of the human body.

## Key facts

- **NIH application ID:** 10275823
- **Project number:** 1R35GM142866-01
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Catherine A Fromen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2021-07-02 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275823

## Citation

> US National Institutes of Health, RePORTER application 10275823, Multiscale considerations for immune engineering at mucosal interfaces (1R35GM142866-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10275823. Licensed CC0.

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