Combined transductional and transcriptional targeting of melanoma cells by artificial virus-like particles.
BACKGROUND
Artificial virus-like particles (AVPs) represent a novel type of liposomal vector resembling retroviral envelopes. AVPs are serum-resistant and non-toxic and can be endowed with a peptide ligand as a targeting device. The vitronectin receptor, alphavbeta3-integrin, is commonly upregulated on malignant melanoma cells. In the present study we investigated whether AVPs carrying cyclic peptides with an RGD integrin binding motif (RGD-AVPs) are suitable for the specific and efficient transduction of human melanoma cells.


METHODS
Plasmid DNA was complexed with low molecular weight non-linear polyethyleneimine and packaged into anionic liposomes. Transduction efficiencies were determined after transient transfection of different cell lines in serum-free medium using green fluorescent protein or luciferase reporter genes.


RESULTS
We demonstrated that RGD-AVPs transduced human melanoma cells with high efficiencies of > 60%. Efficient transduction was clearly dependent on the presence of the cyclic RGD ligand and was selective for melanoma cells. The specificity of the vector system could be further enhanced by using the melanocyte-specific tyrosinase promoter to drive transgene expression.


CONCLUSIONS
Our findings suggest that the AVP technology is a useful approach for generating highly efficient and specific non-viral vectors for melanoma targeting, in particular in a setting of combined transductional and transcriptional targeting.
Nahde
T
T
Institute of Molecular Biology and Tumor Research (IMT), Philipps-University, Marburg, Germany.
Müller
K
K
Fahr
A
A
Müller
R
R
Brüsselbach
S
S
D000595:Amino Acid Sequence; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes; D008545:Melanoma; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D010957:Plasmids; D019030:Receptors, Vitronectin / Q000235:genetics* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured; D014780:Viruses
D008081:Liposomes; D010455:Peptides; D019030:Receptors, Vitronectin; D011993:Recombinant Fusion Proteins