# Targeted Nanotherapy for Pancreatic Cancer

> **NIH NIH R01** · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · 2021 · $323,315

## Abstract

The long-term goal of the proposed research proposal is to develop a targeted paclitaxel nanotherapy that
can be used for the treatment of pancreatic cancer (PanCa) in combination with Gemcitabine (GEM).
Although many conventional and combinational chemotherapies exist to treat PanCa, significant side
effects occur without increasing the survival of patients (not even 2 additional months). Desmoplasia
(characterized by excessive fibrosis and extracellular matrix deposition) causes suboptimal drug delivery in
tumors and thus induces chemo-resistance. Additionally, certain signaling pathways, abnormal tumor cell
membrane lipid structure/composition and restricted drug uptake due to overexpression of drug efflux
associated proteins also lead to cancer progression/metastasis and drug resistance. A recent FDA-
approved (on Sept. 6, 2013) combination treatment regimen [nab-nanoparticles (i.e., paclitaxel nanoparticles,
Abraxane®) plus GEM] has marginally improved (only 1.8 months) overall survival (8.5 months vs. 6.7 months
with GEM alone). Studies have also shown that PTX altered tumor microenvironment (TME) and reduced
desmoplasia, thus improved GEM uptake in pancreatic tumors. We believe that this PTX-mediated
marginally improved therapeutic outcome can be further enhanced by using an inimitable tumor specific
antibody targeted PTX nanoparticle formulation. We hypothesize that antibody-guided, tumor specific
targeted delivery of PPNPs will enhance the bioavailability of PTX in pancreatic tumors and macro/
micro metastatic lesions to attenuate tumor growth and sensitize tumor cells to GEM via decreased
desmoplasia, altered TME and SHH/CXCL12/CXCR4, miR-21 mediated oncogenic signaling pathways.
This proposal examines two levels of targeting PanCa. The first is MUC13 targeted delivery of PTX to
pancreatic tumors as our PPNPs selectively/preferentially reach and accumulate in the tumors/metastatic
lesions. Our preliminary data demonstrates that MUC13 targeted nanoparticles effectively target pancreatic
tumors. The second level of treatment is intravenous administration of GEM. The first level of targeting will
considerably alter TME which will thus promote a better response to GEM. This novel combination therapeutic
modality will enhance drug loading specifically to the tumor site, inducing greater anti-cancer effects while
minimizing side effects. To achieve these goals, three specific aims are proposed: AIM 1: To Evaluate Chemo-
sensitization and TME of PPNPs in PanCa Cells. AIM 2: To Investigate Pharmaco-kinetics/dynamics (PK/PD)
and Safety of PPNPs/GEM in a stromal component containing PanCa xenograft mouse model. AIM 3: To
Evaluate the Therapeutic Efficacy of MUC13 Targeted PPNP Formulation in clinically relevant transgenic
mice and patient derived xenograft (PDX) models. This proposal leads to a better treatment modality by
altering tumor-stromal (paracrine) cross-talk and chemo-sensitization in PanCa which are considered to be
major roadblocks in...

## Key facts

- **NIH application ID:** 9934149
- **Project number:** 5R01CA210192-06
- **Recipient organization:** UNIVERSITY OF TEXAS RIO GRANDE VALLEY
- **Principal Investigator:** Subhash C. Chauhan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,315
- **Award type:** 5
- **Project period:** 2016-06-24 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934149

## Citation

> US National Institutes of Health, RePORTER application 9934149, Targeted Nanotherapy for Pancreatic Cancer (5R01CA210192-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934149. Licensed CC0.

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