title: Metal Chelation Modulates Phototherapeutic Properties of Mitoxantrone-Loaded Porphyrin-Phospholipid Liposomes.
abstract: Liposomes incorporating porphyrin-phospholipid (PoP) can be formulated to release entrapped contents in response to near-infrared (NIR) laser irradiation. Here, we examine effects of chelating copper or zinc into the PoP. Cu(II) and Zn(II) PoP liposomes, containing 10 molar % HPPH-lipid, exhibited unique photophysical properties and released entrapped cargo in response to NIR light. Cu-PoP liposomes exhibited minimal fluorescence and reduced production of reactive oxygen species upon irradiation. Zn-PoP liposomes retained fluorescence and singlet oxygen generation properties; however, they rapidly self-bleached under laser irradiation. Compared to the free base form, both Cu- and Zn-PoP liposomes exhibited reduced phototoxicity in mice. When loaded with mitoxantrone and administered intravenously at 5 mg/kg to mice bearing human pancreatic cancer xenografts, synergistic effects between the drug and the light treatment (for this particular dose and formulation) were realized with metallo-PoP liposomes. The drug-light-interval affected chemophototherapy efficacy and safety.
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York , Buffalo, New York 14260, United States.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Carter
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York , Buffalo, New York 14260, United States.
authors.forename: Sophie
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York , Buffalo, New York 14260, United States.
authors.forename: Jumin
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York , Buffalo, New York 14260, United States.
authors.forename: Dandan
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York , Buffalo, New York 14260, United States.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shao
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York , Buffalo, New York 14260, United States.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lovell
mesh_terms: D000818:Animals; D003300:Copper / Q000737:chemistry; D006801:Humans; D007259:Infrared Rays; D007834:Lasers; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008942:Mitoxantrone / Q000737:chemistry / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010743:Phospholipids / Q000737:chemistry*; D010789:Phototherapy; D011166:Porphyrins / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D015032:Zinc / Q000737:chemistry*
chemical_list: D008081:Liposomes; D010743:Phospholipids; D011166:Porphyrins; D026082:Singlet Oxygen; D003300:Copper; D008942:Mitoxantrone; D015032:Zinc
keywords: Chemophototherapy; light-triggered; liposomes; metalloporphyrins; mitoxantrone; photobleaching; porphyrin-phospholipid; tumor ablation