Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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RESEARCH ARTICLE   (Open Access)
Contents Vol 4 (1)

Polymer-Based Systems for Targeted miRNA Delivery

Oleg Kolosov 1*

+ Author Affiliations

Biosensors and Nanotheranostics 4 (1) 1-8 https://doi.org/10.25163/biosensors.419983

Submitted: 02 December 2024 Revised: 06 February 2025  Published: 10 February 2025 

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Abstract

Background: Star copolymers, composed of a combination of hydrophilic and cationic monomers, are particularly promising for these purposes due to their ability to form stable complexes with nucleic acids. This study investigates the synthesis and characterization of novel star copolymers for nucleic acid delivery. Methods: Five star copolymers and their corresponding five linear diblock precursors were synthesized via Group Transfer Polymerisation (GTP). The copolymers were composed mainly of DMAEMA (a cationic monomer) and PEGMA (a hydrophilic, biocompatible monomer) in varying proportions. A full characterization of the copolymers was performed using Gel Permeation Chromatography (GPC) and H1 NMR spectroscopy to determine MM and composition. The thermoresponsive properties of the copolymers were evaluated through Cloud Point determination, pKa measurement, and Dynamic Light Scattering (DLS) to assess size and zeta potential in aqueous solutions. The copolymers were further tested for their ability to form complexes with DNA at an N/P ratio of 15. Results: All copolymers exhibited thermoresponsive behavior within a temperature range of 31–43 ºC, with a consistent pKa of around 7, independent of MM or composition. The size and zeta potential of the copolymers in deionized water and PBS at pH 7.4 were determined using DLS. Complexes formed between the polymers and DNA were found to have sizes ranging from 24.4 nm to 78.8 nm, with zeta potentials of approximately +10 mV, which falls within the optimal range for successful nucleic acid delivery. Conclusion: The synthesized star copolymers demonstrate promising thermoresponsive behavior and ability to form stable complexes with nucleic acids. Their size and zeta potential indicate potential for use in gene delivery systems, with the observed properties suggesting that the polymers can efficiently encapsulate DNA at an optimal N/P ratio for successful delivery.

Keywords: Star copolymers, Group Transfer Polymerisation, thermoresponsive, pKa, nucleic acid delivery.

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