Photosensitive Poly-l-lysine/Heparin Interpolyelectrolyte Complexes for Delivery of Genetic Drugs.

Viktor Korzhikov-Vlakh,Iuliia Pilipenko,Alina A Manshina,Iuliia Katernuk,Ivan Guryanov,Tatiana B Tennikova,Antonina Lavrentieva,Vladimir Sharoyko

doi:10.3390/polym12051077

Viktor Korzhikov-Vlakh, Iuliia Pilipenko + Show 6 more

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https://doi.org/10.3390/polym12051077

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Journal: Polymers	Publication Date: May 8, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: St Petersburg University, Leibniz University Hannover

Abstract

Photo-triggered release of biopharmaceutical drugs inside the cells is a challenging direction of modern science, which requires obtaining new polymeric systems. The interpolyelectrolyte complexes (IPECs) of poly-l-lysine with heparin capable of encapsulation of genetic constructions—such as model oligonucleotide, siRNA, and pDNA—were obtained. Poly-l-lysine to heparin ratios were optimized to provide the appropriate release kinetics of genetic material from the polyplex. In order to impart the obtained IPEC with photosensitive properties, the linker was synthesized as based on 4-brommethyl-3-nitrobenzoic acid. The conditions and kinetics of photosensitive linker destruction were carefully studied. The colloid particles of IPEC were modified with Cy3 probe and their cellular internalization was investigated by flow cytometry method. The efficacy of photosensitive IPECs as siRNA and pDNA delivery system was evaluated.

Highlights

Gene therapy represents the actual and emerging area of interdisciplinary research, which aims at treatment of wide range of pathologies, from monogenic genetic disorders to inherited and acquired human diseases [1]
It was shown that such complexes have were used to prepare the systems capable of photosensitive release
It was shown that such complexes to contain the excess of heparin over the poly-l-lysine in order to displace the genetic construction from have to contain the excess of heparin over the poly-L-lysine in order to displace the genetic the polyplex

Summary

Introduction

Gene therapy represents the actual and emerging area of interdisciplinary research, which aims at treatment of wide range of pathologies, from monogenic genetic disorders to inherited and acquired human diseases [1]. The main idea of such medical treatment is to deliver missing genes to the cells in order to initiate the synthesis of missing proteins to normalize biochemical processes in the organism. Different types of nucleic acid therapies have been developed: gene sequences for initiation of missing protein synthesis (plasmid DNAs—pDNAs [8] and minicircle DNAs—mcDNAs [9,10]) and those for inhibition of protein translation (small interfering RNAs—siRNAs [11], aptamers [12] and antisense oligonucleotides [13]).

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