# Image Guided Delivery and Evaluation of Low? Density Lipoprotein-Docosahexaenoic acid Nanoparticles for the Management of Hepatocellular Carcinoma

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $370,575

## Abstract

PROJECT SUMMARY/ ABSTRACT
Despite the implementation of surveillance programs for early diagnosis of hepatocelllular carcinoma (HCC),
most patients are currently diagnosed at intermediate or advanced stage of the disease for which there are no
curative interventions. These patients either receive transarterial chemoembolization or the molecular therapy,
sorafenib. While these therapies have proven to prolong survival for some patients, many fail to receive any
benefit due to treatment toxicities, poor liver function or drug resistance. The long term survival for HCC patients
remains poor, with a 5-year survival rates <12%. Novel therapies against HCC are urgently needed as the
incidence of HCC is steadily increasing in the United States. In recent years the natural omega-3 fatty acid,
docosahexaenoic acid (DHA) has been shown to possess promising anticancer properties and its consumption
has been implicated in reducing the risk of HCC. The effects of dietary DHA on established solid tumors is
nominal. To address this issue, our lab has recently engineered a novel low-density lipoprotein (LDL) based
nanoparticle that is reconstituted with unesterified DHA (herein referred to as LDL-DHA). Therapeutically, we
have shown that the LDL-DHA nanoparticle is able to selectively kill rodent HCC cells at doses that do not harm
primary hepatocytes. Furthermore, in a syngeneic rat model of HCC, locoregional delivery of LDL-DHA
nanoparticles (achieved via surgical exposure and catheterization of the hepatic artery) is able to induce
extensive necrosis (>80%) of HCC tumors and impede the tumor growth (3 fold) without injury to surrounding
normal liver. This therapeutic selectivity is germane to HCC, as the background liver disease in intermediate and
advanced HCC is often prone to treatment induced injury. The goal of the present proposal is to evaluate the
utility image-guided minimally invasive locoregional LDL-DHA therapy for the management of HCC. To address
this goal we will examine the following specific aims: 1) Optimize tumor targeting efficacy for catheter-based
locoregional delivery of LDL nanoparticles to HCC under fluoroscopy guidance; 2) Investigate the efficacy of
fluoroscopy-guided locoregional LDL-DHA treatment in inducing tumor necrosis in HCC; 3) Evaluate the role of
amide proton transfer magnetic resonance imaging as a novel molecular imaging approach to quantitatively
assess tumor response to LDL-DHA therapy. At the completion of this project, we expect that the combined
work of these Aims will: (i) optimize the minimal invasive image-guided locoregional delivery of LDL-DHA
nanoparticles to achieve maximum tumor uptake and tumor eradication; and (ii) to noninvasively quantify tumor
response and forecast long term patient outcome following LDL-DHA treatment. The LDL-DHA treatment
strategy will be significant because it offers a new method of treating HCC without secondary injury to the
surrounding liver. Ultimately it is our endeavor to bring...

## Key facts

- **NIH application ID:** 10160811
- **Project number:** 5R01CA215702-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Ian Ronald Corbin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,575
- **Award type:** 5
- **Project period:** 2017-06-07 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160811

## Citation

> US National Institutes of Health, RePORTER application 10160811, Image Guided Delivery and Evaluation of Low? Density Lipoprotein-Docosahexaenoic acid Nanoparticles for the Management of Hepatocellular Carcinoma (5R01CA215702-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10160811. Licensed CC0.

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