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: Yuma Yamada, Yasuo Shinohara, Tomoyuki Kakudo, Shinji Chaki, Shiroh Futaki, Hiroyuki Kamiya, Hideyoshi Harashima
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 303 Issue 1-2 Pg. 1-7 (Oct 13 2005) ISSN: 0378-5173 [Print] Netherlands
• PMID: 16139452 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cholesterol Esters
• Culture Media
• Fluorescent Dyes
• Intercellular Signaling Peptides and Proteins
• Liposomes
• Peptides
• Receptors, Transferrin
• Rhodamines
• Transferrin
• Wasp Venoms
• GALA peptide
• lissamine rhodamine B
• mastoparan
• Cytochromes c

Topics

• Antineoplastic Agents (pharmacology)
• Cell Death
• Cholesterol Esters (chemistry)
• Culture Media (analysis)
• Cytochromes c (analysis, metabolism)
• Cytosol (metabolism)
• Dose-Response Relationship, Drug
• Endocytosis
• Fluorescent Dyes
• Humans
• Hydrogen-Ion Concentration
• Intercellular Signaling Peptides and Proteins
• K562 Cells
• Liposomes (chemistry)
• Mitochondria (drug effects, metabolism)
• Peptides (chemistry, metabolism, pharmacology)
• Receptors, Transferrin (metabolism)
• Rhodamines
• Transferrin (chemistry, metabolism)
• Wasp Venoms (pharmacology)