# Chemophototherapy with Porphyrin-phospholipid Liposomes Permeabilized by Red Light

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $593,755

## Abstract

PROJECT SUMMARY
Pancreatic cancer (PaCa) has the poorest prognosis amongst all major cancer types and claimed the
lives of over 41,000 Americans in 2016. Upon clinical presentation, most patients are diagnosed with
locally advanced disease without good treatment options, either to delay progression or for palliation.
Chemotherapy is generally ineffective due to hypovascular nature of the tumor. Tumor removal is
often unfeasible due to the proximity of major blood vessels, which also complicate thermal ablative
procedures. We seek to develop chemophototherapy as a novel ablative modality for PaCa. This
approach combines phototherapy and chemotherapy using a single agent, based on light-activated
liposomes. Recently, long-circulating liposomal irinotecan (IRI) was approved for treating PaCa. We
have found that when small amounts of porphyrin-phospholipid (i.e. 2 molar percent) are incorporated
into conventional stealth liposomes, stability and long blood-circulating properties are retained. In prior
work using doxorubicin, circulation was >25 hours in rodents, but the liposomes rapidly release their
contents (in a couple of minutes) upon exposure to clinically relevant red light. This results in an order
of magnitude greater drug deposition in the tumor, leading to potent ablation. We will adapt this
approach to develop a long-circulating, light-activated form of irinotecan. We will also apply recent
methodology to develop and assess an ultrafast light-triggered release version, by incorporating small
amounts of unsaturated lipids, together with the PoP. We will assess the IRI PoP formulations in
patient derived xenografts that mimic feathers of the clinical disease, as well as in an orthotopic model
derived from a genetically engineered mouse model of the disease. Treatment parameters such as
the drug dose, light dose, and drug-light interval will be assessed. We will develop and assess
interstitial phototreatment and computer-aided treatment planning of optical fiber placement, based on
MR scans with light propagation modeling that will be required to apply chemophototherapy in clinical
studies. We will characterize the depth of ablation measurements and treatment with multiple
interstitial fibers in large rat tumors. Finally, in order to asses the applicability of this technique near
the critical vessels found in many PaCa tumors, we will characterize drug and light dose functional
responses in large veins in rodents in vivo, in sheep carotid arteries ex vivo and in acellular collagen
vessels.

## Key facts

- **NIH application ID:** 9947917
- **Project number:** 5R01EB017270-07
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Jonathan F Lovell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $593,755
- **Award type:** 5
- **Project period:** 2013-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947917

## Citation

> US National Institutes of Health, RePORTER application 9947917, Chemophototherapy with Porphyrin-phospholipid Liposomes Permeabilized by Red Light (5R01EB017270-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9947917. Licensed CC0.

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