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

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

doi:10.1016/j.msec.2019.110245

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

Mater Sci Eng C Mater Biol Appl. 2020 Jan:106:110245. doi: 10.1016/j.msec.2019.110245. Epub 2019 Oct 10.

Affiliations

¹ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC.
² Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC.
³ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; R&D Center for Membrane Technology, Chung Yuan Christian University, Chungli, Taoyuan 320, Taiwan.
⁴ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC. Electronic address: h.c.tsai@mail.ntust.edu.tw.

PMID: 31753357
DOI: 10.1016/j.msec.2019.110245

Abstract

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.

Keywords: Non-viral carrier; Oligoalkylamine; Polyamidoamine dendrimer; Polyplexes; siRNA.

MeSH terms

Dendrimers / chemistry*
Drug Carriers / chemistry
Ethylenediamines / chemistry*
HeLa Cells
Humans
Magnetic Resonance Spectroscopy
Nylons / chemistry*
Polyamines / chemistry*
RNA, Small Interfering / chemistry*
Spectroscopy, Fourier Transform Infrared

Substances

Dendrimers
Drug Carriers
Ethylenediamines
Nylons
PAMAM-G4
Polyamines
RNA, Small Interfering
diethylenetriamine
tetraethylenepentamine