Abstract
Background: RNA interference is a promising therapeutic tool for the treatment of a variety of diseases, with great potential for cancer therapy. Small interfering RNA (siRNA), however, presents several drawbacks that hamper its therapeutic application. Lipid nanoparticles, including liposomes, are delivery systems with great potential for siRNA delivery, protecting it from degradation, enhancing its cell uptake with the ability of controlled release. However, non-specific delivery and side effects could potentially limit the in vivo application. Therefore, targeting lipid nanoparticles to overexpressed receptors of cancer cells represents a strategy for better therapeutic outcome, with improved efficacy and reduced toxicity. For this purpose, lipid nanoparticles could be functionalized with several moieties that can be recognized by cancer cells more than by normal cells. These ligands include folate, transferrin, peptides, oligosaccharides, monoclonal antibodies and aptamers.
Methods: In this paper, we reviewed functionalization strategies and addressed the major in vitro and in vivo findings in the field of cancer treatment with siRNA.
Results: Many papers showed enhanced siRNA delivery by targeted liposomes, resulting in enhanced drug uptake and better cytotoxicity, with consequent better tumor growth control in xenograft studies.
Conclusion: siRNA delivery mediated by functionalized liposomes is promising, but clinical trials need to be conducted.
Keywords: siRNA, targeting, lipid nanoparticle, liposomes, cancer therapy, toxicity.
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