# Minibeam Radiation Therapy Enhanced Delivery of Nanoparticle Anticancer Agents to Pancreatic Cancer Tumors

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $544,735

## Abstract

PROJECT SUMMARY / ABSTRACT:
 Nanoparticles (NPs) hold great promise for delivering more effective and safer cancer treatment than the
small molecule drugs that are commonly used. This is based on studies reporting that these agents can
potentially achieve greater exposure in solid tumors. However, these promises are largely hampered by a low
and inefficient tumor uptake in which only 5-10% of NPs in the plasma are actually distributed from plasma to
solid tumors. Certain tumors, such as pancreatic cancer (PaCa), have even greater inherent barriers to the
tumor delivery of NPs. Thus, there is a strong need to discover methods that can significantly and safely enhance
the overall delivery of NPs to tumors. Our overall hypothesis is that induction minibeam radiation therapy (MRT),
a novel radiation treatment, is such a method. Whereas, conventional broad beam radiation (BRT) only
moderately enhances drug delivery to tumors (0.2- to 2-fold). MRT is an experimental radiation therapy with
unique spatial and dosimetric characteristics that are drastically different from conventional BRT. Solid
preclinical studies have demonstrated that MRT is capable of an ultra-high therapeutic ratio. We recently
discovered that MRT, in contrast to BRT, modifies tumor vasculature and increases tumor perfusion. We
hypothesize that we can take advantage of the changes in tumor perfusion induced by MRT to significantly and
safely enhance NP delivery to tumors compared to NPs alone or after BRT. This hypothesis is supported by our
extensive results in genetically engineered mouse models (GEMMs) of breast cancer where induction MRT prior
to administration of PEGylated liposomal doxorubicin (Doxil®; PLD) enhanced the delivery of PLD to tumors by
an unprecedented magnitude of 6- to 10-fold and the enhancement was sustained safely with weekly treatments.
In addition, MRT produced a 4-fold greater increase in the tumor delivery of PLD to GEMMs of breast cancer,
which was associated with higher levels of overall and PD-L1 expressing macrophages compared to BRT. Our
2nd pilot study in PaCa GEMMs showed that MRT was able to increase the tumor exposure of PEG-liposomal
irinotecan (Onivyde®, FDA approved for PaCa treatment) and its active metabolite SN38 by >4-fold compared to
Onivyde alone. This grant will allow us to translate our ground breaking MRT results to PaCa where the barriers
to NP delivery are extensive, surgical resection is the only curative option but only 15% of patients have
resectable disease and the MRT + NP regimen would be ideal for pre-surgical neoadjuvant treatment of PaCa.
 This work will be performed by a multidisciplinary research team using novel models, technologies and FDA
approved drugs that can be readily translated to clinical trials in 3 aims over 5 yrs: AIM 1. Evaluate induction
MRT-enhanced delivery of NP anticancer drugs in GEMMs of PaCa; AIM 2. Investigate mechanistic effects of
induction MRT-enhanced tumor delivery of NPs in GEMMs of PaCa; AIM 3...

## Key facts

- **NIH application ID:** 10380681
- **Project number:** 5R01CA247652-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** SHA X CHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $544,735
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380681

## Citation

> US National Institutes of Health, RePORTER application 10380681, Minibeam Radiation Therapy Enhanced Delivery of Nanoparticle Anticancer Agents to Pancreatic Cancer Tumors (5R01CA247652-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10380681. Licensed CC0.

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