Details

Autor(en) / Beteiligte

• Hanurry, Endiries Yibru
• Hsu, Wei-Hsin
• Darge, Haile Fentahun
• Birhan, Yihenew Simegniew
• Mekonnen, Tefera Worku
• Andrgie, Abegaz Tizazu
• Chou, Hsiao-Ying
• Cheng, Chih-Chia
• Lai, Juin-Yih
• Tsai, Hsieh-Chih

Titel

In vitro siRNA delivery via diethylenetriamine- and tetraethylenepentamine-modified carboxyl group-terminated Poly(amido)amine generation 4.5 dendrimers

Ist Teil von

• Materials Science & Engineering C, 2020-01, Vol.106, p.110245-110245, Article 110245

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• The recent discovery of small interfering RNAs (siRNAs) has opened new avenues for designing personalized treatment options for various diseases. However, the therapeutic application of siRNAs has been confronted with many challenges because of short half-life in circulation, poor membrane penetration, difficulty in escaping from endosomes, and insufficient release into the cytosol. To overcome these challenges, we designed a diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA)-modified polyamidoamine dendrimer generation 4.5 (PDG4.5), and characterized it using 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy (COSY), heteronuclear single–quantum correlation spectroscopy (HSQC), and Fourier transform infrared (FTIR) spectroscopy followed by conjugation with siRNA. The PDG4.5-DETA and PDG4.5-TEPA polyplexes exhibited spherical nanosize, ideal zeta potential, and effective siRNA binding ability, protected the siRNA from nuclease attack, and revealed less cytotoxicity of PDG4.5-DETA and PDG4.5-TEPA in HeLa cells. More importantly, the polyplexes also revealed good cellular internalization and facilitated translocation of the siRNA into the cytosol. Thus, PDG4.5-DETA and PDG4.5-TEPA can act as potential siRNA carriers in future medical and pharmaceutical applications. [Display omitted] •The binding of siRNA with dendrimers effectively form nanosized, spherical and stable polyplexes.•The Modified dendrimers protect the siRNA against nuclease enzymes.•The fluorescence microscopic analyses confirm the dissemination of siRNA throughout the entire cytoplasm.•The amine groups assist the endosomal escape of polyplexes before lysosome degradation.