# Development of multifunctional drug and immune modulator delivery nanoparticles for the treatment of cancer patients with comorbid atherosclerosis

> **NIH NIH R01** · EMORY UNIVERSITY · 2023 · $532,237

## Abstract

Project Summary
Cancer and cardiovascular disease are leading causes of death in the United States. Given the high percentage
of cancer patients with co-existing atherosclerosis, the development of cancer therapeutics that prevent
progression of atherosclerosis have the potential to align cancer therapy goals with favorable cardiovascular
outcomes. Hyaluronic acid (HA) has unique properties that are desirable for the development of biocompatible
and biodegradable nanoparticle drug delivery systems for both cancer and atherosclerosis. We have developed
a hyaluronic acid nanoparticle (HANP) conjugated with PD1 memetic peptides that target and block immune
checkpoint protein PD-L1 and carry the cholesterol-lowering drug Avasimibe (PD1Y-HANP/Ava). Avasimibe is a
multifunctional agent that decreases cholesterol accumulation, inhibits tumor cell growth, and enhances immune
response by activating cytotoxic T cells. We found that systemic administrations of PD1Y-HANP/Ava led to
targeted delivery into tumors and atherosclerotic plaques, inhibition of tumor growth and atherosclerosis
progression, and significant improvement in mouse survival in a dual mouse cancer and atherosclerosis model.
In this study, we hypothesize that systemic delivery of urokinase plasminogen activator receptor (uPAR), PD-
L1 and CD44 co-targeted HANP carrying Avasimibe (ATF/PD1Y-HANP/Ava) leads to the efficient delivery of the
HANP/Ava into tumors and atherosclerotic plaques, resulting in a significant anti-tumor growth effect by direct
inhibition of tumor cell proliferation, activation of cytotoxic CD8+ T cells, and pro-immune modulatory effect of
ATF/PD1Y-HANP/Ava in tumor microenvironment. We further hypothesize that delivery of targeted PD1Y-
HANP/Ava into atherosclerotic plaques decreases cholesterol-rich macrophages and infiltrating immune cells,
and thereby prevents atherosclerosis progression. To develop and validate the proposed immunotherapy, we
will first develop ATF/PD1Y-HANP/Ava and examine the efficiency of targeted delivery in metastatic mouse colon
cancer models (Aim 1). Therapeutic efficacy and immune responses following targeted PD1Y-HANP/Ava
treatment, alone or in combination with a chemotherapy drug, irinotecan, will be evaluated in the mouse cancer
models (Aim 1). We will then determine the effect of the targeted PD1Y-HANP/Ava on targeted delivery, immune
responses and therapeutic efficacy in tumor and atherosclerotic plaques in a dual mouse colon cancer and
atherosclerosis model (Aim 2). Immunological analysis of tumors and atherosclerotic plaques will allow us to
determine therapy-related changes in immune cell types and functions, especially CD8+ T cell activity. We will
then investigate the feasibility of translation in cancer patients by examining targeted delivery and direct cytotoxic
effect of the targeted PD1Y-HANP/Ava in colon cancer patient derived xenograft models (Aim 3). Finally,
pharmacokinetics, toxicity, biodistribution and systemic immune resp...

## Key facts

- **NIH application ID:** 10548149
- **Project number:** 5R01CA257861-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Lily Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $532,237
- **Award type:** 5
- **Project period:** 2021-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10548149

## Citation

> US National Institutes of Health, RePORTER application 10548149, Development of multifunctional drug and immune modulator delivery nanoparticles for the treatment of cancer patients with comorbid atherosclerosis (5R01CA257861-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10548149. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*