title: Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes.
abstract: In this work, the in vitro anti-Leishmania activity of photodynamic liposomes made of soybean phosphatidylcholine, sodium cholate, total polar archaeolipids (TPAs) extracted from the hyperhalophile archaea Halorubrum tebenquichense and the photosensitizer zinc phthalocyanine (ZnPcAL) was compared to that of ultradeformable photodynamic liposomes lacking TPAs (ZnPcUDLs). We found that while ZnPcUDLs and ZnPcALs (130 nm mean diameter and -35 mV zeta potential) were innocuous against promastigotes, a low concentration (0.01 μM ZnPc and 7.6 μM phospholipids) of ZnPcALs irradiated at a very low-energy density (0.2 J/cm(2)) eliminated L. braziliensis amastigotes from J774 macrophages, without reducing the viability of the host cells. In such conditions, ZnPcALs were harmless for J774 macrophages, HaCaT keratinocytes, and bone marrow-derived dendritic cells. Therefore, topical photodynamic treatment would not likely affect skin-associated lymphoid tissue. ZnPcALs were extensively captured by macrophages, but ZnPcUDLs were not, leading to 2.5-fold increased intracellular delivery of ZnPc than with ZnPcUDLs. Despite mediating low levels of reactive oxygen species, the higher delivery of ZnPc and the multiple (caveolin- and clathrin-dependent plus phagocytic) intracellular pathway followed by ZnPc would have been the reason for the higher antiamastigote activity of ZnPcALs. The leishmanicidal activity of photodynamic liposomal ZnPc was improved by TPA-containing liposomes.
authors.affiliation: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Perez
authors.affiliation: Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
authors.forename: Agustina
authors.initials: A
authors.lastname: Casasco
authors.affiliation: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Priscila
authors.initials: P
authors.lastname: Schilrreff
authors.affiliation: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina ; Unidad Operativa Sistemas de Liberación Controlada, Centro de Investigación y Desarrollo en Química, Instituto Nacional de Tecnología Industrial (INTI), Buenos Aires, Argentina.
authors.forename: Maria Victoria Defain
authors.initials: MV
authors.lastname: Tesoriero
authors.affiliation: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Luc
authors.initials: L
authors.lastname: Duempelmann
authors.affiliation: Virology Institute, Center for Research in Veterinary and Agronomic Sciences, National Institute for Agricultural Technology (INTA), Hurlingham, BA, Argentina.
authors.forename: Juan Sebastián
authors.initials: JS
authors.lastname: Pappalardo
authors.affiliation: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Maria Julia
authors.initials: MJ
authors.lastname: Altube
authors.affiliation: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Leticia
authors.initials: L
authors.lastname: Higa
authors.affiliation: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Morilla
authors.affiliation: Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Petray
authors.affiliation: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Buenos Aires, Argentina.
authors.forename: Eder L
authors.initials: EL
authors.lastname: Romero
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005995:Glyceryl Ethers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D054833:Isoindoles; D007891:Leishmania / Q000187:drug effects* / Q000528:radiation effects*; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D017967:Zinc Compounds
chemical_list: D000981:Antiprotozoal Agents; D005995:Glyceryl Ethers; D007211:Indoles; D054833:Isoindoles; D008081:Liposomes; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D017967:Zinc Compounds; C094417:archaeol lipid; C052159:Zn(II)-phthalocyanine
keywords: Leishmania amastigotes; Zn intracellular delivery; irradiation; macrophages