Waleed Mohammed-Saeid1,2, Jackson Chitanda3, Mays Al-Dulaymi1, Ronald Verrall4, Ildiko Badea5. 1. Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Health Sciences Building, Room 3D01.5, Saskatoon, Saskatchewan, S7N 5E5, Canada. 2. College of Pharmacy, Taibah University, Medina, Saudi Arabia. 3. Department of Chemical and Biological Engineering, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 4. Department of Chemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. 5. Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Health Sciences Building, Room 3D01.5, Saskatoon, Saskatchewan, S7N 5E5, Canada. ildiko.badea@usask.ca.
Abstract
PURPOSE: We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy. METHODS: Integrin receptor targeting peptide, cyclic-arginylglycylaspartic acid (cRGD), was either chemically coupled to a gemini surfactant backbone or physically co-formulated with lipoplexes. Several formulations and transfection techniques were developed. Transfection efficiency and cellular toxicity of the lipoplexes were evaluated in an in vitro human melanoma model. Physicochemical properties were examined using dynamic light scattering, zeta-potential, and small-angle X-ray scattering measurements. RESULTS: RGD-modified gemini surfactant based lipoplexes showed significant enhancement in gene transfection activity in A375 cell lines compared to the standard non-targeted formulation, especially when RGD was chemically conjugated to the gemini surfactant (RGD-G). The RGD had no effect on the cell toxicity profile of the lipoplex systems. Targeting specificity was confirmed by using an excess of free RGD and negative control peptide (RAD) and was demonstrated by using normal human epidermal keratinocytes. Physicochemical characterization showed that all nanoparticles were in the optimal size range for cellular uptake and there were no significant differences between RGD-modified and standard lipoplexes. CONCLUSIONS: These findings indicate the potential of RGD-modified gemini surfactant-based lipoplexes for use in melanoma gene therapy as an alternative to conventional chemotherapy.
PURPOSE: We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy. METHODS: Integrin receptor targeting peptide, cyclic-arginylglycylaspartic acid (cRGD), was either chemically coupled to a gemini surfactant backbone or physically co-formulated with lipoplexes. Several formulations and transfection techniques were developed. Transfection efficiency and cellular toxicity of the lipoplexes were evaluated in an in vitro humanmelanoma model. Physicochemical properties were examined using dynamic light scattering, zeta-potential, and small-angle X-ray scattering measurements. RESULTS: RGD-modified gemini surfactant based lipoplexes showed significant enhancement in gene transfection activity in A375 cell lines compared to the standard non-targeted formulation, especially when RGD was chemically conjugated to the gemini surfactant (RGD-G). The RGD had no effect on the cell toxicity profile of the lipoplex systems. Targeting specificity was confirmed by using an excess of free RGD and negative control peptide (RAD) and was demonstrated by using normal human epidermal keratinocytes. Physicochemical characterization showed that all nanoparticles were in the optimal size range for cellular uptake and there were no significant differences between RGD-modified and standard lipoplexes. CONCLUSIONS: These findings indicate the potential of RGD-modified gemini surfactant-based lipoplexes for use in melanoma gene therapy as an alternative to conventional chemotherapy.
Authors: Stephanie E A Gratton; Patricia A Ropp; Patrick D Pohlhaus; J Christopher Luft; Victoria J Madden; Mary E Napier; Joseph M DeSimone Journal: Proc Natl Acad Sci U S A Date: 2008-08-12 Impact factor: 11.205
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Authors: P A Van Belle; R Elenitsas; K Satyamoorthy; J T Wolfe; D Guerry; L Schuchter; T J Van Belle; S Albelda; P Tahin; M Herlyn; D E Elder Journal: Hum Pathol Date: 1999-05 Impact factor: 3.466
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