title: Mitochondrial delivery of mastoparan with transferrin liposomes equipped with a pH-sensitive fusogenic peptide for selective cancer therapy.
abstract: Mastoparan (MP), a potent facilitator of mitochondrial permeability transition (PT), could be used as an antitumor agent, if it were encapsulated in a tumor selective delivery system. We recently developed transferrin-modified liposomes (Tf-L) with a pH-sensitive fusogenic peptide (GALA), which delivers an encapsulated fluorescent marker into cytosol efficiently. In this study, we encapsulated MP into Tf-L with GALA for the selective delivery to mitochondria of tumor cells. The MP showed potent PT activity at concentrations above 25 microM in a homogenate of K 562 cells as well as in isolated mitochondria in the presence of phosphate. Tf-L equipped with cholesteryl GALA can release encapsulated sulforhodamine B, while Tf-L failed, as evidenced by confocal laser scanning microscopy. The MP, which was delivered with Tf-L with GALA, released cytochrome c (cyt c) from mitochondria to the cytosol, while free MP released cyt c not only to the cytosol but also extracellulary. These results demonstrate the utility of MP in Tf-L with GALA for cancer therapy.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Sapporo 060-0812, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakudo
authors.forename: Shinji
authors.initials: S
authors.lastname: Chaki
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiya
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death; D002788:Cholesterol Esters / Q000737:chemistry; D003470:Culture Media / Q000032:analysis; D045304:Cytochromes c / Q000032:analysis / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins; D020014:K562 Cells; D008081:Liposomes / Q000737:chemistry*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011990:Receptors, Transferrin / Q000378:metabolism; D012235:Rhodamines; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism; D014862:Wasp Venoms / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002788:Cholesterol Esters; D003470:Culture Media; D005456:Fluorescent Dyes; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D010455:Peptides; D011990:Receptors, Transferrin; D012235:Rhodamines; D014168:Transferrin; D014862:Wasp Venoms; C066951:GALA peptide; C022027:lissamine rhodamine B; C037500:mastoparan; D045304:Cytochromes c