Abstract
Cancer is one of the most important problems of modern medicine. At the present time, gene therapy has been developed against cancer, which includes the delivery of anticancer small interfering RNAs (siRNAs) directed at cancer proteins. The prospect of creating drugs based on RNA interference implies the use of delivery systems. Metal nanoparticles are the most studied objects for medicine, including their application as non-viral vectors. We have synthesized gold nanoparticles (AuNPs) modified with cationic carbosilane dendrons of 1–3 generations, with a positive charge on the surface, gold nanoparticles can effectively bind small interfering RNAs. Using a photometric viability test and flow cytometry, we assessed the ability of dendronized gold nanoparticles in delivering siRNAs to tumor cells. The efficiency of the complexes in initiating apoptosis was measured and, also, the overall effect of proapoptotic siRNA on cells. AuNP15 has both the highest efficacy and toxicity. The delivery efficiency in suspension cell lines was 50–60%. Complexes with targeted siRNA decreased cell viability by 20% compared to control and initiated apoptosis.
Highlights
Oncological disorders remain one of the main problems in medicine
Non-fluorescent siRNAs were used for cytotoxicity assay; siRNAs labeled with FAM (6-Carboxyfluorescein, IPOC NASB, Minsk, Belarus) at the 50 -end of the sense sequence were used in flow cytometric experiments
Different signals from the threshold were observed at concentrations of 75 μg/mL and higher
Summary
Can be the resistance of some types of cancer to chemotherapy and radiation therapy. Against this backdrop, researchers continue to search for effective solutions for cancer therapy. One possible approach could be the use of short-chain non-coding RNAs, namely microRNAs (miRNAs) and siRNAs [1,2]. SiRNAs are short (20–25 base pairs) double-stranded nucleotides that silence genes due to specific binding to matrix RNA, and as a result block the synthesis of target proteins [3,4]. A significant family among these proteins is bcl, normally, this protein regulates mitochondrial activity, promotes the release of cytochrome C and the formation of reactive oxygen species (ROS). It is assumed that the mutation of bcl could be
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