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
Christina M. MacLaughlin, Lili Ding, Cheng Jin, Pingjiang Cao, Iram Siddiqui, David M. Hwang, Juan Chen, Brian C. Wilson, Gang Zheng, and David W. Hedley, "Porphyrin lipid nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model," Proc. SPIE 9696, Molecular-Guided Surgery: Molecules, Devices, and Applications II, 96960F (Presented at SPIE BiOS: February 13, 2016; Published: 4 March 2016); https://doi.org/10.1117/12.2214882.
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