# Engineering Immunomodulatory Nanoscale Coatings for Protecting Islet Transplants

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $346,821

## Abstract

Project Summary
Clinical islet transplantation (CIT), the infusion of allogeneic islets into the liver, has shown significant promise in
the long-term treatment of Type I diabetes by providing a cell-based means to mimic the normal physiological
response to glucose. While promising, it is dampened by the impaired function and loss of islets following
implantation. This loss is attributed to strong inflammatory and immunological responses to the transplant,
primarily instigated by cell surface proteins and antigens. While polymeric encapsulation has shown strong
potential in murine models, clinical translational of this approach is poor. Insufficient clinical efficacy is attributed
to the significant nutritional deficiencies imposed by standard microencapsulation, as well as immunorecognition
and subsequent innate and adaptive responses to the foreign graft. In this proposal, we seek to shift this standard
encapsulation paradigm by incorporating both innovative nano-scale polymeric coatings and novel
functionalization strategies to distinctly modulate immune responses. With evidence that encapsulation can be
highly synergistic with immunomodulatory agents, we seek to generate bioactive, immunomodulatory coatings
through bio-orthogonal chemistry that serves to not only to mask donor cell surface proteins but also direct the
local immune response towards a tolerogenic phenotype through the generation of a supportive milieu. We
hypothesize that the polymer grafting of islets to express functional handles for the conjugation of
immunomodulatory agents and/or nanoparticles will enhance islet engraftment and functional duration by both
masking host recognition of surface antigens and generating a local immunoregulatory environment to support
the long-term survival of the transplanted islets. To test this hypothesis, immunomodulatory agents will be bio-
orthogonally tethered to nano-scale coatings on the islet surface and screened for their capacity to skew host
immune responses towards tolerogenic phenotypes in vitro and in diabetic murine models (Aim 1). Further, to
generate a supportive graft microenvironment and protective coating, reactive oxygen species (ROS)
nanoparticles will be into nano-scale coatings (Aim 2). Using innovative in vitro screening platforms, ideal
immunomodulatory coatings will be selected, with subsequent validation in diabetic murine models. The design
of effective strategies to combine stable nano-scale coatings with local immunomoduation could significantly
improve the efficacy and long-term stability of islet transplants in the absence of chronic, systemic
immunosuppression.

## Key facts

- **NIH application ID:** 10142609
- **Project number:** 1R01DK126413-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Cherie L Stabler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,821
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142609

## Citation

> US National Institutes of Health, RePORTER application 10142609, Engineering Immunomodulatory Nanoscale Coatings for Protecting Islet Transplants (1R01DK126413-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10142609. Licensed CC0.

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