# Highly Functional Organic Core Templated High-Density Lipoproteins to Reverse Vascular Disease

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2020 · $197,500

## Abstract

PROJECT SUMMARY
Cholesterol has been linked to several cardiac and brain vascular diseases, dementias, diabetes, and cancer.
Emerging data suggests that such diseases can be traced back to an imbalance in cholesterol transport
mediated by high-density lipoproteins (HDLs), specifically attributed to reduced amount and function of native
HDLs. As such, synthetic HDL nanoparticles (HDL NPs) have been proposed as next-generation therapeutics
for treating these diseases. However, because the development of materials has lagged far behind the pace of
biological discovery and understanding, costly failures in the clinic have resulted, reinforcing the desperate
need for new approaches to HDL-inspired therapies. To be successful, synthetic HDL NPs must accurately
mimic native HDLs in size, shape, cholesterol-uptake capacity, and functional capacity required to manipulate
and transport cellular cholesterol in an effective manner. To this end, we are seeking to develop, for the first
time, a synthetic strategy to tune HDL NPs so that their form and function can be exquisitely and optimally
manipulated around a set of parameters defined by native HDLs. To that end, we have constructed a bio-
inspired HDL NP mimetic by assembling the HDL-defining apolipoprotein A-I (apo A-I) and phospholipids
around multifunctional organic core (MOC) templates. This approach appears to be highly promising, as these
organic HDL NPs (OHDL NPs) closely mimic natural HDLs in their size (~10 nm) and ability to efflux
cholesterol from lipid-laden macrophages. Here we propose to optimize the synthesis and purification of OHDL
NPs, through modulation of the MOC and downstream synthetic steps, characterize the OHDL NPs, quantify
the ability of OHDL NPs to efflux and influx cholesterol and reduce inflammation in vitro, and reduce
atherosclerotic plaque burden in a mouse model of atherosclerosis. Through these studies we will generate an
optimal OHDL NP therapeutic for the modulation of cholesterol flux, and demonstrate both in vitro and in vivo
the efficacy of OHDL NPs at reducing inflammation and atherosclerotic plaque formation.

## Key facts

- **NIH application ID:** 9900703
- **Project number:** 5R21AG062999-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** SonBinh TheBao Nguyen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,500
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900703

## Citation

> US National Institutes of Health, RePORTER application 9900703, Highly Functional Organic Core Templated High-Density Lipoproteins to Reverse Vascular Disease (5R21AG062999-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/9900703. Licensed CC0.

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