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Design and Evaluation of RGD-Modified Gemini Surfactant-Based Lipoplexes for Targeted Gene Therapy in Melanoma Model

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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.

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Abbreviations

cRGD:

Cyclic-arginylglycylaspartic acid

DOPE:

Phosphatidylethanolamine

GFP:

Green fluorescent protein

IFN-γ:

Interferon-gamma

SAXS:

Small-angle X-ray scattering

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Acknowledgments and Disclosures

The authors report no conflicts of interest. The authors are grateful for financial support from NSERC and SHRF to conduct this study.

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Authors and Affiliations

  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

    Waleed Mohammed-Saeid, Mays Al-Dulaymi & Ildiko Badea

  2. College of Pharmacy, Taibah University, Medina, Saudi Arabia

    Waleed Mohammed-Saeid

  3. Department of Chemical and Biological Engineering, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    Jackson Chitanda

  4. Department of Chemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    Ronald Verrall

Authors
  1. Waleed Mohammed-Saeid
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  2. Jackson Chitanda
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  3. Mays Al-Dulaymi
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  4. Ronald Verrall
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  5. Ildiko Badea
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Corresponding author

Correspondence to Ildiko Badea.

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Mohammed-Saeid, W., Chitanda, J., Al-Dulaymi, M. et al. Design and Evaluation of RGD-Modified Gemini Surfactant-Based Lipoplexes for Targeted Gene Therapy in Melanoma Model. Pharm Res 34, 1886–1896 (2017). https://doi.org/10.1007/s11095-017-2197-0

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  • DOI: https://doi.org/10.1007/s11095-017-2197-0

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