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Proceedings Paper

Porphyrin lipid nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model
Author(s): Christina M. MacLaughlin; Lili Ding; Cheng Jin; Pingjiang Cao; Iram Siddiqui; David M. Hwang; Juan Chen; Brian C. Wilson; Gang Zheng; David W. Hedley
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Paper Abstract

Local disease control is a major problem in the treatment of pancreatic cancer, because curative-intent surgery is only possible in a minority of patients, and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for ablation of pancreatic tumors, this approach remains under investigated. Using photothermal sensitizers in combination with laser light for PTT can result in more efficient conversion of light energy to heat, and confinement of thermal destruction to the tumor, thus sparing adjacent organs and vasculature. Porphyrins have been previously employed as photosensitizers for PDT and PTT, however their incorporation in to “porphysomes”, lipid-based nanoparticles each containing ~80,000 porphyrins through conjugation of pyropheophorbide to phospholipids, carries two distinct advantages: 1) high-density porphyrin packing imparts the nanoparticles with enhanced photonic properties for imaging and phototherapy; 2) the enhanced permeability and retention effect may be exploited for optimal delivery of porphysomes to the tumor region thus high payload porphyrin delivery. The feasibility of porphysome-enhanced PTT for pancreatic cancer treatment was investigated using a patient-derived orthotopic pancreas xenograft tumor model. Uptake of porphysomes at the orthotopic tumor site was validated using ex vivo fluorescence imaging of intact organs of interest. The accumulation of porphysomes in orthotopic tumor microstructure was also confirmed by fluorescence imaging of excised tissue slices. PTT progress was monitored as changes in tumor surface temperature using IR optical imaging. Histological analyses were conducted to examine microstructure changes in tissue morphology, and the viability of remaining tumor tissues following exposure to heat. These studies may also provide insight as to the contribution of heat sink in application of thermal therapies to highly vascularized pancreatic tumors.

Paper Details

Date Published: 4 March 2016
PDF: 12 pages
Proc. SPIE 9696, Molecular-Guided Surgery: Molecules, Devices, and Applications II, 96960F (4 March 2016); doi: 10.1117/12.2214882
Show Author Affiliations
Christina M. MacLaughlin, Univ. Health Network (Canada)
Univ. of Toronto (Canada)
Princess Margaret Hospital (Canada)
Lili Ding, Univ. Health Network (Canada)
Cheng Jin, Univ. Health Network (Canada)
Univ. of Toronto (Canada)
Pingjiang Cao, Univ. Health Network (Canada)
Iram Siddiqui, Univ. Health Network (Canada)
David M. Hwang, Univ. Health Network (Canada)
Juan Chen, Univ. Health Network (Canada)
Brian C. Wilson, Univ. Health Network (Canada)
Univ. of Toronto (Canada)
Princess Margaret Hospital (Canada)
Gang Zheng, Univ. Health Network (Canada)
Univ. of Toronto (Canada)
David W. Hedley, Univ. Health Network (Canada)
Univ. of Toronto (Canada)
Princess Margaret Hospital (Canada)

Published in SPIE Proceedings Vol. 9696:
Molecular-Guided Surgery: Molecules, Devices, and Applications II
Brian W. Pogue; Sylvain Gioux, Editor(s)

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