Non-viral lipid-based nanoparticles for targeted cancer systemic gene silencing.
New molecular biology techniques have uncovered the hidden role of genes in cancer. Identification of activated oncogenes, as fundamental genetic differences relative to normal cells, has made it possible to consider such genes as targets for antitumor therapy, namely by applying gene silencing strategies. In this regard, antisense oligonucleotides or small interfering RNAs, constitute promising therapeutic tools. The widespread clinical application of such molecules as modulators of gene expression, is still dependent on several aspects that limit their bioavailability, including: enhanced biological stability, favourable pharmacokinetics, enhanced tumor cell uptake and, consequently, efficient targeted delivery. One of the most promising strategies to overcome the barriers faced by gene silencing molecules, upon systemic administration, involves the use of lipid-based nanoparticles. The first part of this review aims at providing the reader with the molecular mechanism of action of the most important gene silencing molecules used in anticancer therapy. The primary obstacle for translating gene silencing technology from an effective research tool into a feasible therapeutic strategy remains its efficient delivery to the targeted cell type in vivo. Therefore, an overview of different lipid-based strategies for nucleic acid delivery will be presented on the second part. As we learn more about the pharmacokinetics and pharmacodynamics of the carrier and/or of the gene silencing molecules, it will be possible to further improve the delivery strategy that likely in the future will lead to the ideal non-viral particle for targeted cancer systemic gene silencing.
Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, Rua do Norte, University of Coimbra, 3000-295 Coimbra, Portugal.
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Moreira
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Santos
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Moura
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Pedroso de Lima
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D000818:Animals; D020868:Gene Silencing; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles; D009369:Neoplasms / Q000098:blood supply / Q000628:therapy; D034741:RNA, Small Interfering
D008055:Lipids; D034741:RNA, Small Interfering