# Anti-vascular and cytotoxic nanoparticle formulations for ovarian cancer therapy

> **NIH NIH R01** · BROOKLYN COLLEGE · 2021 · $121,408

## Abstract

Ovarian cancer (OC) has the highest mortality rate of all cancers of the female reproductive system and
outcomes have not changed over the past four decades. This year, over 20,000 women will be diagnosed with
OC in the United States more than 14,000 women will die from this disease. Platinum-based therapy is the
main therapeutic option for OC patients and ultimately, systemic toxicity limits the dosage given and this, in
part, limits its effectiveness. To overcome this therapeutic roadblock, alternative routes of administration have
been sought and include the practically difficult intraperitoneal (IP) injection, and more recently, the emerging
strategy of combining Pt (II) chemotherapy with tumor vasculature-targeting agents. The overarching goal of
this study is to develop a nanoparticle (NP)-based therapy for targeted delivery of high dose Pt (II) and a
vascular disrupting agent directly to cancer cells and endothelium, to enhance treatment outcomes. As proof-
of-principle, we have chosen combretastatin CA4 as the vascular targeting agent. Our proposal explores a
second generation, slow releasing polymer NP platform, with poly(lactic-co-glycolic) (PLGA) acid core
encapsulating Pt (II) and CA4. The NP’s coating is comprised of a RGDFFF peptide that stabilizes the NP and
simultaneously serves as a targeting ligand to αvβ3 integrin via its RGD moiety. The PLGA is FDA-approved
and amino acids of the peptide have Generally Regarded As Safe (GRAS) status. The NP is completely
biodegradable. Encapsulation of Pt (II) and CA4 will reduce systemic toxicity and allow us to explore the use of
effectively higher dosages than currently feasible. Upon the NP’s accumulation in the tumor interstitium, via
enhanced permeability and retention (EPR) effects, the cellular NPs uptake will be enhanced via receptor-
mediated endocytosis. The effect of the cytotoxic activity of Pt (II) and CA4 towards cancer cells and the
tumor’s vasculature, will be measured through therapeutic outcomes. A small percentage of near infrared
fluorophore (NIRF) will be incorporated into the NP’s coating to enable noninvasive optical imaging. The
combination of therapeutic and diagnostic features will transform the NP into a “theranostic” platform. In vitro
studies will include evaluation of NPs targeting to cancer cells, their biological activity, and compatibility with
the immune system. In vivo studies will focus on the assessment of NPs pharmacologic parameters, tumor
targeting, tolerability, and, finally, therapeutic efficacy. Combined in vitro and in vivo studies will employ
microscopy, immunochemistry, and histology, to define the best NP-based treatment regimen resulting in
therapeutic outcomes rivaling free drug routines currently used in the clinic. Thus, the proposed specific aims
are:
Aim 1: Synthesize and characterize an RGDFFF-coated NP platform for targeting, visualizing and treating
ovarian cancer. Aim 2: Test targeting efficacy and therapeutic potential of CA4-NPs and P...

## Key facts

- **NIH application ID:** 10411413
- **Project number:** 3R01CA238539-03S1
- **Recipient organization:** BROOKLYN COLLEGE
- **Principal Investigator:** JOHN A MARTIGNETTI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $121,408
- **Award type:** 3
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411413

## Citation

> US National Institutes of Health, RePORTER application 10411413, Anti-vascular and cytotoxic nanoparticle formulations for ovarian cancer therapy (3R01CA238539-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10411413. Licensed CC0.

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