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Published on: May 2, 2019
Non-Viral Systems Based on PAMAM-Calix-Dendrimers for Regulatory siRNA Delivery into Cancer Cells
Pavel Padnya1, Igor Shiabiev1, Dmitry Pysin1
1A.M. Butlerov Chemistry Institute, Kazan Federal University, 18 Kremlyovskaya Str., 420008 Kazan, Russia.
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.
Insights
Symmetrical polyamidoamine dendronized thiacalix[4]arenes effectively deliver gene therapy for cancer treatment. These novel nanocarriers show reduced toxicity and protect therapeutic nucleic acids, advancing nanomedicine development.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Molecular Biology
Background:
- Cancer is a leading cause of death in developed nations.
- Gene therapy, particularly RNA interference, shows promise for cancer treatment.
- Effective delivery vectors are crucial for nucleic acid-based therapies, driving research into novel nanomaterials.
Purpose of the Study:
- To investigate the potential of symmetrical polyamidoamine dendronized thiacalix[4]arenes (PAMAM-calix-dendrimers) as nanocarriers for gene therapy.
- To evaluate the ability of PAMAM-calix-dendrimers to complex with small interfering RNAs (siRNAs).
- To assess the safety and efficacy of these novel dendrimers in delivering gene material to cancer cells.
Main Methods:
- Synthesis and characterization of PAMAM-calix-dendrimers.
- Complexation studies with siRNAs.
- In vitro evaluation of siRNA protection against enzymatic degradation.
- Assessment of gene delivery efficiency in HeLa cells.
- Comparative analysis of PAMAM-calix-dendrimers and classical PAMAM dendrimers.
Main Results:
- PAMAM-calix-dendrimers formed stable, positively charged complexes with siRNAs.
- These complexes effectively protected siRNAs from degradation.
- Efficient delivery of gene material to HeLa cells was demonstrated.
- A unique inverse relationship between generation number and cytotoxicity was observed, with no toxicity at effective concentrations.
Conclusions:
- PAMAM-calix-dendrimers are effective and low-toxicity nanocarriers for siRNA delivery.
- These dendrimers offer a promising platform for developing advanced gene delivery systems.
- The findings support the advancement of nanomedicine for cancer therapy.
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