A dual targeting dendrimer-mediated siRNA delivery system for effective gene silencing in cancer therapy.
Authors of this article are:
Dong Y, Yu T, Ding L, Laurini E, Huang Y, Zhang M, Weng Y, Lin S, Chen P, Marson D, Jiang Y, Giorgio S, Pricl S, Liu X, Rocchi P, Peng L.
A summary of the article is shown below:
Small interfering RNA (siRNA) is emerging as novel therapeutics for treating various diseases, provided a safe and efficient delivery is available. In particular, specific delivery to target cells is critical for achieving high therapeutic efficacy while reducing toxicity. Amphiphilic dendrimers are emerging as novel promising carriers for siRNA delivery by virtue of the combined multivalent cooperativity of dendrimers with the self-assembling property of lipid vectors. Here, we report a ballistic approach for targeted siRNA delivery to cancer cells using an amphiphilic dendrimer equipped with dual targeting peptide bearing RGDK warhead. According to the molecular design, the amphiphilic dendrimer was expected to perform effective siRNA delivery while the targeting peptide was to home in on tumors via interaction of its warhead with integrin and the neuropilin-1 receptor on cancer cells. Coating the positively charged siRNA/dendrimer delivery complex with the negatively charged segment of the targeting peptide via electrostatic interactions led to small and stable nanoparticles able to protect siRNA from degradation, maintain accessibility of RGDK for targeting cancer cells, and preserve endosome escape capacity. The targeted system had enhanced siRNA delivery, stronger gene silencing and more potent anticancer activity compared to non-targeted or covalent dendrimer-based systems. In addition, neither acute toxicity nor induced inflammation was observed. Consequently, this delivery system constitutes a promising nonviral vector for targeted delivery and can be further applied for elaborating RNAi-based personalized medicine against cancer. Our study also demonstrates that nanotechnology based on self-assembling dendrimers can contribute new perspectives in various biomedical applications.
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