# Reprogramming Tumor Microenvironment by Nanoparticle

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $338,550

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with a notoriously
dismal prognosis and is the 4th leading cause of cancer related deaths in the United States. Unfortunately, 80-
85% patients are diagnosed with unresectable, incurable advanced stage tumors putting the median survival at
<6 months and the overall 5-year survival at <5%. Therefore, new therapeutic strategies are urgently needed
to improve the dismal outcome in PDAC patients.
PDAC is characterized by a robust desmoplastic reaction. Desmoplastic reaction endows PDAC with a unique
microenvironment that promotes tumor growth, metastasis and resists tumor cells to chemotherapy,
collectively resulting in a dismal prognosis. Hence, new treatment strategies are urgently needed to inhibit
desmoplasia where nanotechnology could play a pivotal role. Although the mechanism is still not clear and
slowly emerging, a number of PCC/PSC secreted factors are recognized to play critical roles facilitating
bidirectional crosstalk between PCCs and PSCs that promotes desmoplasia. We demonstrate in the
preliminary data that AuNP inhibits proliferation of both PCCs and PSCs and efficiently disrupts the PCC-PSC
crosstalk by reducing secretion of a number of critical factors. Therefore, AuNP provides potential opportunities
to improve the dismal prognosis in PDAC by simultaneously inhibiting multiple pathways involved in
desmoplasia. We also demonstrate in the preliminary data that an AuNP-based targeted drug delivery system
efficiently targets and inhibits proliferation of both PCCs and PSCs exploiting overexpression of EGFR in these
cells. Since the overproduction of -SMA positive PSCs which sometimes account for ~90 % of the total
fibrotic mass, depletion of both PSCs and PCCs by AuNP-based targeted drug delivery system is expected to
reduce the extent of cross talk and cut down the formation of the huge fibrotic tissue. Decrease in fibrotic mass
will allow better drug penetration and delivery, thereby increasing drug sensitivity. Furthermore,
nanoconjugates having higher circulation time will soak the fibrotic mass for a longer duration and hence
penetrate more efficiently into the fibrotic tissue. Therefore, in the present proposal, we will use a two-pronged
approach; 1) disrupting PCC-PSC crosstalk by gold nanoparticle alone and understanding the molecular
mechanism, and 2) depleting both PCC and PSC by an AuNP-based targeted drug delivery system to inhibit
desmoplasia. We will use three specific aims to accomplish these objectives; Aim 1: Interrogating disruption of
PCC-PSC crosstalk by gold nanoparticles; Aim 2: Disrupting PCC-PSC cross-talk tuning pharmacokinetics of
a targeted drug delivery system; Aim 3: Improving gemcitabine therapy by reprogramming tumor
microenvironment by gold nanoparticle.
 After decades of ineffective therapeutic strategies against the epithelial component in PDAC, it is only
recently realized that the massive stromal tissue is not an inn...

## Key facts

- **NIH application ID:** 9828764
- **Project number:** 5R01CA213278-04
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Priyabrata Mukherjee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $338,550
- **Award type:** 5
- **Project period:** 2016-12-22 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828764

## Citation

> US National Institutes of Health, RePORTER application 9828764, Reprogramming Tumor Microenvironment by Nanoparticle (5R01CA213278-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9828764. Licensed CC0.

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