Combined transductional and transcriptional targeting of melanoma cells byartificial 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 devi ce. The vitronectin receptor, alpha (v)beta (3)-integrin, is commonly upreg ulated on malignant melanoma cells. in the present study we investigated wh ether AVPs carrying cyclic peptides with an RGD integrin binding motif (RGD -AVPs) are suitable for the specific and efficient transduction of human me lanoma cells. Methods Plasmid DNA was complexed with low molecular weight non-linear poly ethyleneimine and packaged into anionic liposomes. Transduction efficiencie s were determined after transient transfection of different cell lines in s erum-free medium using green fluorescent protein or luciferase reporter gen es. 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 t he melanocyte-specific tyrosinase promoter to drive transgene expression. Conclusion Our findings suggest that the AVP technology is a useful approac h for generating highly efficient and specific non-viral vectors for melano ma targeting, in particular in a setting of combined transductional and tra nscriptional targeting. Copyright (C) 2001 John Wiley & Sons, Ltd.