title: Porphysome nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model: a pilot study.
abstract: Local disease control is a major challenge in pancreatic cancer treatment, because surgical resection of the primary tumor is only possible in a minority of patients and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for focal ablation of pancreatic tumors, this approach remains underinvestigated. Using photothermal sensitizers in combination with laser light irradiation for PTT can result in more efficient conversion of light energy to heat and improved spatial confinement of thermal destruction to the tumor. Porphysomes are self-assembled nanoparticles composed mainly of pyropheophorbide-conjugated phospholipids, enabling the packing of ∼80,000 porphyrin photosensitizers per particle. The high-density porphyrin loading imparts enhanced photonic properties and enables high-payload tumor delivery. A patient-derived orthotopic pancreas xenograft model was used to evaluate the feasibility of porphysome-enhanced PTT for pancreatic cancer. Biodistribution and tumor accumulation were evaluated using fluorescence intensity measurements from homogenized tissues and imaging of excised organs. Tumor surface temperature was recorded using IR optical imaging during light irradiation to monitor treatment progress. Histological analyses were conducted to determine the extent of PTT thermal damage. These studies may provide insight into the influence of heat-sink effect on thermal therapy dosimetry for well-perfused pancreatic tumors.
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, CanadabUniversity of Toronto, Department of Medical Biophysics, 101 College Street, Toronto, Ontario M5G 1L7, CanadacPrincess Margaret Hospital, Department of Medical Oncology and Hematology, 610 University Avenue, Toronto, Ontario M5T 2M9, Canada.
authors.forename: Christina M
authors.initials: CM
authors.lastname: MacLaughlin
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, CanadabUniversity of Toronto, Department of Medical Biophysics, 101 College Street, Toronto, Ontario M5G 1L7, CanadadUniversity of Toronto, Department of Pharmaceutical Sciences, 144 College Street, Toronto, Ontario M5T 2M9, Canada.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jin
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Pingjiang
authors.initials: P
authors.lastname: Cao
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Iram
authors.initials: I
authors.lastname: Siddiqui
authors.affiliation: University Health Network, Department of Pathology, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Hwang
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, CanadabUniversity of Toronto, Department of Medical Biophysics, 101 College Street, Toronto, Ontario M5G 1L7, CanadacPrincess Margaret Hospital, Department of Medical Oncology and Hematology, 610 University Avenue, Toronto, Ontario M5T 2M9, Canada.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, CanadabUniversity of Toronto, Department of Medical Biophysics, 101 College Street, Toronto, Ontario M5G 1L7, CanadadUniversity of Toronto, Department of Pharmaceutical Sciences, 144 College Street, Toronto, Ontario M5T 2M9, Canada.
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.affiliation: University Health Network, Princess Margaret Cancer Center, 101 College Street, Toronto, Ontario M5G 1L7, CanadabUniversity of Toronto, Department of Medical Biophysics, 101 College Street, Toronto, Ontario M5G 1L7, CanadacPrincess Margaret Hospital, Department of Medical Oncology and Hematology, 610 University Avenue, Toronto, Ontario M5T 2M9, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Hedley
mesh_terms: D064593:Heterografts; D006801:Humans; D066298:In Vitro Techniques; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000628:therapy*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D010789:Phototherapy / Q000379:methods*; D010865:Pilot Projects; D014018:Tissue Distribution
chemical_list: D017319:Photosensitizing Agents