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Lipid nanocapsule functionalization by lipopeptides derived from human papillomavirus type-16 capsid for nucleic acid
M Weyland1, A Griveau, J Bejaud
1Inserm U1066, Micro et nanomédecines biomimétiques, F-49933 Angers, France.
Abstract:
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.
Insights
Biomimetic lipid nanocapsules functionalized with a L1 papillomavirus type-16 lipopeptide show promise for cancer therapy. These L1-LNCs effectively deliver small interfering RNAs (siRNAs) to repress targeted messengers in cancer cells.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- Plasmid DNA (pDNA) and small interfering RNAs (siRNAs) are crucial for cancer treatment but face delivery challenges due to charge and degradation.
- Viral vectors are effective but elicit immunogenicity, while synthetic nanoparticles offer lower immunogenicity but less efficient delivery.
- Developing non-viral, non-immunogenic delivery systems for nucleic acids is critical for advancing cancer therapeutics.
Purpose of the Study:
- To develop and evaluate biomimetic lipid nanocapsules (LNCs) functionalized with a L1 papillomavirus type-16 capsid-derived lipopeptide for nucleic acid delivery.
- To investigate the complexation and transfection capabilities of these L1-peptide-functionalized LNCs (L1-LNCs) in U87MG glioma and Caco-2 colorectal adenocarcinoma cells.
- To assess the potential of L1-LNCs for delivering both pDNA and siRNAs for cancer therapy.
Main Methods:
- Lipid nanocapsules (LNCs) were synthesized and functionalized with a L1 papillomavirus type-16 derived lipopeptide.
- Complexation assays were performed to evaluate the binding of L1-LNCs with plasmid DNA (pDNA) and small interfering RNAs (siRNAs).
- Transfection efficiency of pDNA-L1-LNC and siRNA-L1-LNC complexes was assessed in U87MG and Caco-2 cell lines.
Main Results:
- L1-LNCs successfully complexed with both pDNA and siRNAs.
- pDNA-L1-LNC complexes exhibited limited transfection efficiency in the tested cell lines.
- siRNA-L1-LNC complexes demonstrated significant efficacy in repressing targeted messenger RNAs, indicating successful gene silencing.
Conclusions:
- Biomimetic L1-LNCs are capable of complexing with nucleic acids and show potential as non-viral delivery vectors.
- While pDNA delivery was inefficient, siRNA-L1-LNC complexes proved effective for targeted gene silencing in cancer cells.
- These findings highlight the potential of L1-LNCs for siRNA-based cancer therapeutics, offering a non-immunogenic and efficient delivery strategy.
