Non-Viral Systems Based on PAMAM-Calix-Dendrimers for Regulatory siRNA Delivery into Cancer Cells
Pavel Padnya, Igor Shiabiev, Dmitry Pysin, Tatiana P. Gerasimova, Bahdan Ranishenka, Alesia Stanavaya, Viktar Abashkin, Dzmitry Shcharbin, Xiangyang Shi, Mingwu Shen, Anastasia Nazarova, Ivan I. Stoikov
Abstract
Cancer is one of the most common diseases in developed countries. Recently, gene therapy has emerged as a promising approach to cancer treatment and has already entered clinical practice worldwide. RNA interference-based therapy is a promising method for cancer treatment. However, there are a number of limitations that require vectors to deliver therapeutic nucleic acids to target tissues and organs. Active research is currently underway to find highly effective, low-toxic nanomaterials capable of acting as nanocarriers. In this study, we demonstrated for the first time the ability of symmetrical polyamidoamine dendronized thiacalix[4]arenes (PAMAM-calix-dendrimers) to form stable positively charged complexes with siRNAs, protect them from enzymatic degradation, and efficiently deliver gene material to HeLa cells. A distinctive feature of PAMAM-calix-dendrimers was the unusual decrease in hemo- and cytotoxicity with increasing generation, while these compounds did not cause toxic effects at concentrations required for siRNA binding and delivery. A comparative analysis of the efficiency of complex formation of PAMAM-calix-dendrimers and classical PAMAM dendrimers with siRNAs was also performed. The findings may facilitate the creation of novel unique gene delivery systems for cancer nanomedicine development.