# Image-guided ultrasound therapy and drug delivery in pancreatic cancer

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $650,148

## Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and invasive cancer, with a median
survival of 6 months and a 5-year survival rate of 6%. Although recent advances have been
made in the understanding of PDAC development, effective therapies are lacking. At the time of
diagnosis, less than 15% of patients qualify for surgery due to the presence of locally advanced
disease and micrometastases. Here, we consider an alternative paradigm in which ultrasound
therapy (ablation or hyperthermia) of the primary tumor is combined with systemic drug delivery
particles and immunotherapy that can effectively treat remaining primary tumor and metastases.
We hypothesize that ultrasound therapy of pancreatic cancer, performed in combination with
delivery of gemcitabine nanoparticles (squalene-gemcitabine nanoassemblies (Sq-Gem-NAs))
and immunotherapy, can effectively and safely treat pancreatic cancer. We recently
demonstrated 50 fold enhancement of delivery of nanoparticles to the ablated margin in tumor
models that span epithelial cancer and highly invasive mesenchymal phenotypes. We further
demonstrated enhanced survival combining hyperthermia with drug and immunotherapy; we
extend the result in preliminary data to show complete regression of systemic cancer. We also
demonstrate the synthesis of squalene-gemcitabine conjugates and their self-assembly as
nanoparticles. Squalene-gemcitabine conjugation is known to extend the circulation of the
intact drug and the conjugate has greater efficacy than free drug in resistant cancers. Further,
we have synthesized a positron emission tomography chelator conjugated to squalene to be
used to assess the pharmacokinetics and biodistribution of the particles with and without
ultrasound therapy. Such particles can be targeted to pancreatic cancer and can be long
circulating or temperature sensitive. The combination of an immune adjuvant (CpG) with a
checkpoint inhibitor (aPD-1) is incorporated and response shown to be enhanced by ultrasound
therapy. Our specific aims are therefore to: 1) fabricate and characterize Sq-Gem-NAs and Sq-
BAT conjugates and evaluate their self-assembly with other lipids, 2) determine the
biodistribution of Sq-Gem NAs with and without plectin-1 targeted moieties and ultrasound in
both healthy mice and mice with PDAC tumors and 3) compare the therapeutic response of
PDAC mice treated with the Sq-Gem-NAs and ultrasound and immunotherapy protocols. Both
ablation and hyperthermia ultrasound protocols will be evaluated.

## Key facts

- **NIH application ID:** 9968147
- **Project number:** 5R01CA210553-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Katherine W Ferrara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $650,148
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968147

## Citation

> US National Institutes of Health, RePORTER application 9968147, Image-guided ultrasound therapy and drug delivery in pancreatic cancer (5R01CA210553-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968147. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*