Lipid nanocapsule functionalization by lipopeptides derived from human papillomavirus type-16 capsid for nucleic acid delivery into cancer cells.
Plasmid DNA (pDNA) and small interfering RNAs (siRNAs) are very useful tools for the treatment of cancer. However, pDNA and siRNAs efficacy is restricted by their negative charge and susceptibility to degradation by endonucleases that prevent them penetrating tissue and cellular barriers such as the plasma and endolysosomal membranes. Viral vectors have some advantages but their use is largely limited by their immunogenicity. On the other hand, synthetic nanoparticles have advantage of being relatively non-immunogenic but their ability to deliver nucleic acids remains less efficient than their viral counterparts. The present study is focussed on the development and evaluation of biomimetic lipid nanocapsules (LNCs) functionalized with a L1 papillomavirus type-16 capsid-derived lipopeptide on their surface, for transfection of U87MG glioma cells and Caco-2 colorectal adenocarcinoma cells with pDNA or siRNAs. Since the L1-peptide has been described as a nuclear localization signal able to complex with nucleic acids and bind to heparan sulfate on the cell surface, the structure and function of L1-peptide bound to LNCs (L1-LNCs) were investigated. Although L1-LNCs were shown to complex with both pDNA and siRNAs, the pDNA-L1-LNC complexes showed only weak transfection efficiency. In contrast, siRNA-L1-LNC complexes appeared as effective repressors of targeted messengers.
['Weyland|M|M|', 'Griveau|A|A|', 'Bejaud|J|J|', 'Benoit|J-P|JP|', 'Coursaget|P|P|', 'Garcion|E|E|']
D000071916:AC133 Antigen D000818:Animals D015703:Antigens, CD D019556:COS Cells D036022:Capsid Proteins D045744:Cell Line, Tumor D002522:Chlorocebus aethiops D004247:DNA D006023:Glycoproteins D006801:Humans D008055:Lipids D055666:Lipopeptides D053769:Nanocapsules D009369:Neoplasms D009856:Oncogene Proteins, Viral D010455:Peptides D010957:Plasmids D019253:Proto-Oncogene Proteins c-bcl-2 D034741:RNA, Small Interfering
Cancer DNA siRNA Vectorization Nanoparticles Papillomavirus derived peptide