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Design and Evaluation of RGD-Modified Gemini Surfactant-Based Lipoplexes for Targeted Gene Therapy in Melanoma Model
- Source :
- Pharmaceutical Research. 34:1886-1896
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy. 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. 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. These findings indicate the potential of RGD-modified gemini surfactant-based lipoplexes for use in melanoma gene therapy as an alternative to conventional chemotherapy.
- Subjects :
- Keratinocytes
0301 basic medicine
Integrins
Genetic enhancement
Integrin
Pharmaceutical Science
Peptide
Transfection
Peptides, Cyclic
Cell Line
Surface-Active Agents
03 medical and health sciences
Drug Delivery Systems
0302 clinical medicine
Dynamic light scattering
Pulmonary surfactant
Cell Line, Tumor
medicine
Humans
Pharmacology (medical)
Melanoma
Pharmacology
chemistry.chemical_classification
biology
Chemistry
Organic Chemistry
DNA
Genetic Therapy
medicine.disease
Lipids
Molecular biology
In vitro
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Biophysics
Molecular Medicine
lipids (amino acids, peptides, and proteins)
Plasmids
Biotechnology
Subjects
Details
- ISSN :
- 1573904X and 07248741
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Pharmaceutical Research
- Accession number :
- edsair.doi.dedup.....38162950cbd7ab967c74cc340d846d3f