# Inflammation-targeted delivery of corticosteroids using genetically engineered cellular nanoparticles

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $197,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Bacterial pneumonia causes severe local inflammation in the lungs that can result in serious complications if left
unchecked. While antibiotics are oftentimes an effective treatment, drug-resistant bacteria that do not respond
to the standard of care represent a major threat. Bacteria contain a number of pathogen-associated molecular
patterns that are highly efficient at activating the immune system, and the overproduction of proinflammatory
factors can have deleterious effects such as causing the air sacs within the lungs to become filled with fluid. To
address these negative effects, corticosteroids have been employed as an adjunct therapy in combination with
antibiotic treatment. There is clinical evidence that supplemental anti-inflammatories can reduce patient morbidity
and mortality, and the beneficial effects are the most pronounced in cases of severe disease. Despite their
advantages, steroids are broadly immunosuppressive and cannot be administered at high dosages or over
extended periods of time without side effects. In this proposal, our goal is to employ a genetic engineering
approach for creating a next-generation a cellular nanoparticle (CNP) platform that can specifically target sites
of inflammation. CNPs are an emerging class of nanocarrier that utilize the principles of biomimicry, and they
have demonstrated considerable promise for drug delivery applications. Their fabrication involves the coating of
synthetic nanoparticulate cores with naturally derived cellular membrane, which provides an inherently
multifunctional and multi-antigenic layer of camouflage. We will further advance the CNP concept by genetically
engineering the nanoparticles to express specific membrane-bound targeting proteins. Leveraging the fact that
activated endothelial cells at sites of inflammation upregulate their expression of cell adhesion molecules, CNPs
will be fabricated using cell membrane that has been engineered to express the cognate ligands. Each
inflammation-targeting CNP formulation will be loaded with corticosteroids, delivering the payloads precisely to
where they are most needed. By improving the therapeutic index of these drugs, we hope to prevent the harmful
effects associated with excessive inflammation while reducing any treatment-related side effects. If successful,
this approach could potentially be applied across a wide range of inflammation-driven pathologies.

## Key facts

- **NIH application ID:** 10646914
- **Project number:** 1R21AI175904-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Ronnie H Fang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $197,500
- **Award type:** 1
- **Project period:** 2023-02-08 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10646914

## Citation

> US National Institutes of Health, RePORTER application 10646914, Inflammation-targeted delivery of corticosteroids using genetically engineered cellular nanoparticles (1R21AI175904-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10646914. Licensed CC0.

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