# Polymeric Nanomaterials for Probing and Modulating Innate Immune Responses

> **NIH NIH R35** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2022 · $398,750

## Abstract

Abstract:
Inflammation is a defense mechanism triggered by innate immune system against any foreign invasion to restore
homeostasis, but when it sustains for a prolonged period of several months to years, it transforms into a chronic
condition resulting in several harmful diseases. The inflammasome is a hetero-multimeric protein complex known
for activating inflammatory caspases followed by subsequent processing of cytokines, which makes it one of the
key players during inflammation. Abnormal activation of inflammasomes can initiate undesirable inflammatory
responses associated with the progression of chronic inflammatory diseases. Several studies have investigated
nanomaterial interactions with immune cells to understand their role in various biological applications and tailor
them to different needs. Indeed, several types of nanomaterials have been widely explored to target the immune
cells at the disease site to modulate the immune responses. However, our recent studies and several recent
reports suggest that many of these nanomaterials activate inflammasomes in immune cells non-specifically,
potentially exacerbating the disease. But the comprehensive characterization of the nanomaterial-immune cell
interactions that results in inflammasome activation and the unwanted innate immune response is poorly studied
due to a lack of appropriate investigative tools. The overall vision of my research program is to design
immunoengineering platforms bridging nanoscience and engineering design with manipulation of the immune
system to address fundamental and translational questions in immunology. We focus on developing effective
immunotherapy strategies by understanding the interactions between different immune system components,
between various nanomaterials and immune cells. Specifically, we aim to address fundamental questions in
inflammasome biology and how nanomaterial properties affect their interactions with innate immune cells and
inflammasome activation. To accomplish this, we propose to engineer a library of multiparametric polymeric
nanomaterial platform with various surface and core characteristics in a single system. This will allow us to test
the effect of these nanomaterial properties on inflammasome activation, tweaking one property at a time to
develop nanomaterial structure-property-function relationships. We have developed novel high-throughput
imaging platform to enable monitoring of inflammasome activation in real time. We have also engineered novel
imaging probes to monitor inflammasome activation in vivo in real time. Using these tools, over next five years,
we aim to understand the interactions between nanomaterials (polymer-based) and immune cells (macrophages,
monocytes, dendritic cells and neutrophils) in the context of inflammasome activation and uncover the
mechanisms of this activation in vitro and in vivo. In summary, the information obtained from these studies could
provide design criteria that guide the development of next...

## Key facts

- **NIH application ID:** 10499713
- **Project number:** 1R35GM147019-01
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Ashish A. Kulkarni
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,750
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499713

## Citation

> US National Institutes of Health, RePORTER application 10499713, Polymeric Nanomaterials for Probing and Modulating Innate Immune Responses (1R35GM147019-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499713. Licensed CC0.

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