# Exploiting gold nanoparticle as a probe to identify therapeutic targets

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $78,953

## Abstract

Nanoparticles (NPs) have mostly been used as delivery vehicles for various biomedical applications. When
exposed to biological fluids NPs interact with proteins forming a biological coating on their surface, termed protein
corona. Protein corona around NPs have been investigated to address the biological responses including
biodistribution, clearance and potential toxicity of NP. Previously, we along with others have demonstrated self-
therapeutic property of gold nanoparticles (GNPs). In the current application, exploiting self-therapeutic GNP
(ST-GNP) as a probe, we are proposing a unique concept of capturing, identifying and validating therapeutic
targets responsible for tumor growth and therapy resistance in cancer.
 We demonstrated that ST-GNP inhibited functions of a number of tumor-promoting heparin-binding
growth factors (HB-GFs) via binding through the HB-domain that altered protein conformations, whereas
conformations and functions of non-HB-GFs remained unaltered. In addition, among various sizes, GNP of 20
nm size demonstrated highest therapeutic efficacy whereas GNP of 100 nm size was non self-therapeutic (NST-
GNP). Importantly, ST-GNP inhibited tumor growth, metastasis and sensitized ovarian cancer cells to cisplatin
by reversing epithelial-mesenchymal transition (EMT) and abrogating MAPK-signaling (Fig 1) In orthotopic
model of pancreatic cancer, we reported that ST-GNP disrupted cross-talk between cancer cells and cancer
associated fibroblasts (CAFs) and reprogrammed tumor microenvironment that inhibited tumor growth.
Investigating protein enrichment on ST-GNP from ovarian cancer or normal cellular lysates, we identified
SMNDC1 and PPA1, as potential new targets for tumor growth. Furthermore, we recently reported that non-toxic
Auroliposome enhanced silencing efficacy of siRNA and more effectively inhibited ovarian tumor growth
compared to traditional DOTAP-DOPE based liposomal delivery of siRNA. Based on these results, we
hypothesize that functions of the proteins enriched on ST-GNP will be inhibited resulting in tumor growth
inhibition and therapy resistance. Therefore, these ST-GNP-enriched proteins may serve as potential therapeutic
targets. We will use specific aims below to test our hypothesis;
Specific aim 1: Investigating protein enrichment on ST-GNP.
Specific aim 2: Validating therapeutic targets in animal models.
Impact: Protein corona around NPs is evolving as a unique signature for personalized medicine. Our findings
support that the ST-GNP could be utilized to identify therapeutic targets not only for ovarian and pancreatic
cancer but in diabetic retinopathy, macular degeneration and rheumatoid arthritis as well where others have
reported ST property of GNP to inhibit angiogenesis in these models.

## Key facts

- **NIH application ID:** 10746440
- **Project number:** 5R01CA260449-03
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Resham Bhattacharya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $78,953
- **Award type:** 5
- **Project period:** 2021-12-15 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10746440

## Citation

> US National Institutes of Health, RePORTER application 10746440, Exploiting gold nanoparticle as a probe to identify therapeutic targets (5R01CA260449-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10746440. Licensed CC0.

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