Francesca Sacchetti1, Gaetano Marverti2, Domenico D'Arca2, Leda Severi1, Eleonora Maretti1, Valentina Iannuccelli1, Salvatore Pacifico3, Glauco Ponterini1, Maria Paola Costi1, Eliana Leo4. 1. Department of Life Science, University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy. 2. Department Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Via Campi, 287, Modena, Italy. 3. Department of Pharmaceutical Sciences, University of Ferrara, via Fossato di Mortara 17-19, 44100, Ferrara, Italy. 4. Department of Life Science, University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy. eliana.leo@unimore.it.
Abstract
PURPOSE: To evaluate the potential effects of PEGylated pH-sensitive liposomes on the intracellular activity of a new peptide recently characterized as a novel inhibitor of the human thymidylate synthase (hTS) over-expressed in many drug-resistant human cancer cell lines. METHODS: Peptide-loaded pH-sensitive PEGylated (PpHL) and non-PEGylated liposomes (nPpHL) were carefully characterized and delivered to cis-platinum resistant ovarian cancer C13* cells; the influence of the PpHL on the drug intracellular activity was investigated by the Western Blot analysis of proteins involved in the pathway affected by hTS inhibition. RESULTS: Although PpHL and nPpHL showed different sizes, surface hydrophilicities and serum stabilities, both carriers entrapped the drug efficiently and stably demonstrating a pH dependent release; moreover, the different behavior against J774 macrophage cells confirmed the ability of PEGylation in protecting liposomes from the reticuloendothelial system. Comparable effects were instead observed against C13* cells and biochemical data by immunoblot analysis indicated that PEGylated pH-sensitive liposomes do not modify the proteomic profile of the cells, fully preserving the activity of the biomolecule. CONCLUSION: PpHL can be considered as efficient delivery systems for the new promising anti-cancer peptide.
PURPOSE: To evaluate the potential effects of PEGylated pH-sensitive liposomes on the intracellular activity of a new peptide recently characterized as a novel inhibitor of the humanthymidylate synthase (hTS) over-expressed in many drug-resistant humancancer cell lines. METHODS: Peptide-loaded pH-sensitive PEGylated (PpHL) and non-PEGylated liposomes (nPpHL) were carefully characterized and delivered to cis-platinum resistant ovarian cancer C13* cells; the influence of the PpHL on the drug intracellular activity was investigated by the Western Blot analysis of proteins involved in the pathway affected by hTS inhibition. RESULTS: Although PpHL and nPpHL showed different sizes, surface hydrophilicities and serum stabilities, both carriers entrapped the drug efficiently and stably demonstrating a pH dependent release; moreover, the different behavior against J774 macrophage cells confirmed the ability of PEGylation in protecting liposomes from the reticuloendothelial system. Comparable effects were instead observed against C13* cells and biochemical data by immunoblot analysis indicated that PEGylated pH-sensitive liposomes do not modify the proteomic profile of the cells, fully preserving the activity of the biomolecule. CONCLUSION: PpHL can be considered as efficient delivery systems for the new promising anti-cancer peptide.
Entities:
Keywords:
PEGylation; anti-cancer peptides; intracellular protein modulation; pH-sensitive liposomes; western blot
Authors: Martin Lundqvist; Johannes Stigler; Giuliano Elia; Iseult Lynch; Tommy Cedervall; Kenneth A Dawson Journal: Proc Natl Acad Sci U S A Date: 2008-09-22 Impact factor: 11.205
Authors: C Allen; N Dos Santos; R Gallagher; G N C Chiu; Y Shu; W M Li; S A Johnstone; A S Janoff; L D Mayer; M S Webb; M B Bally Journal: Biosci Rep Date: 2002-04 Impact factor: 3.840