Pentapeptide YIGSR-mediated HT-1080 fibrosarcoma cells targeting of adriamycin encapsulated in sterically stabilized liposomes.
In the peptide-targeted therapy for cancer, peptides are used to reach a selective and specific target in cancer cells. Peptides are used free or coupled to chemotherapeutic drugs, phagues, proteins, polymers, liposomes, and polymer-grafted liposomes. Using this latter approach, the pentapeptide YIGSR was coupled to the distal end from carboxyl groups of liposome-grafted polyethyleneglycol (PEG) chains (YIGSR-PEG-liposome). As a control, the peptide PEAGD coupled to PEG-liposome was used. The biological activity of YIGSR-PEG-liposome was tested using HT-1080 human fibrosarcoma cells. In adhesion assays, the YIGSR-PEG-liposome coated to plastic plates promoted 30% of the specific cell attachment. In competition assays, YIGSR-PEG-liposome inhibited the specific attachment of cells to laminin-1-coated plates by 25%. Following this, we prepared peptide-PEG-liposomes encapsulating adriamycin (ADR). In vitro cytotoxicity assays against HT-1080 cells gave IC(50) values 2.1 times lower for YIGSR-PEG-liposomal ADR in comparison to PEAGD-PEG-liposomal ADR. The free peptide added in excess increased the IC(50) value of YIGSR-PEG-liposomal ADR by 72%, while the IC(50) value of control liposomal ADR was unaffected, supporting a receptor-mediated mechanism of targeting. In addition, the lower IC(50) value is correlated with a higher total of ADR accumulation in the cells.
Departament de Cancer & Metastasis, Institut de Recerca Oncologica, Gran Via, Km 2,7. L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain 08907. lalopez@aecom.yu.edu
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D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D008081:Liposomes / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007797:Laminin; D008081:Liposomes; D009842:Oligopeptides; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; D011092:Polyethylene Glycols; D004317:Doxorubicin