Influence of Polymer Backbone Architecture and Amino Group Density on the Cytotoxicity and Transfection Performance of Cationic Block Copolymer Polyplexes
- 1Laboratory for Chemical Design of Bionanomaterials, Faculty of Chemistry, M.V. Lomonosov Moscow State University, 117234 Moscow, Russia
- 2Faculty of Chemistry, Shenzhen MSU-BIT University, Shenzhen 518100, China
Abstract
The development of efficient and biocompatible polymeric vectors remains a cornerstone of successful gene therapy. In this study, we developed a versatile polymeric platform for nucleic acid delivery by synthesizing a series of cationic block copolymers based on polyaspartamide or polyglutamide backbones and polyethylene glycol (PEG) segments. Block copolymer precursors were synthesized via ring-opening polymerization. The degrees of polymerization were confirmed via 1H NMR spectroscopy, followed by functionalization with diethylenetriamine, spermine, or spermidine. Cytotoxicity was evaluated using the WST-1 assay in HEK293 and SH-SY5Y cells. Cytotoxicity profiling identified N3-PEG114-b-pAsp(DET)62 as the least cytotoxic polymer among the tested derivatives in both cell lines. The polyplexes enhanced reporter gene expression compared with naked plasmid DNA, and an N/P ratio of 15 was selected for subsequent comparative experiments. In SH-SY5Y neuroblastoma cells, the material obtained following the dopamine-modification procedure exhibited a 1.78-fold increase in reporter fluorescence and a 1.75-fold increase in the percentage of GFP-positive cells compared with the corresponding unmodified formulation. These findings establish the engineered block copolymers as highly adaptable, low-toxicity, and efficient candidates for targeted nucleic acid delivery and support the potential of dopamine functionalization for enhancing delivery to dopamine-receptor-expressing cells.
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BibTeX
@article{kozyrev2026influence,
title = {{Influence of Polymer Backbone Architecture and Amino Group Density on the Cytotoxicity and Transfection Performance of Cationic Block Copolymer Polyplexes}},
author = {Nikita A. Kozyrev and Alexey V. Doroshchenko and Anna D. Lapanik and Natalia L. Klyachko and Anton V. Lopukhov},
journal = {Polymers},
year = {2026},
month = oct,
doi = {10.3390/polym18212671},
url = {https://www.mdpi.com/2073-4360/18/21/2671},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Influence of Polymer Backbone Architecture and Amino Group Density on the Cytotoxicity and Transfection Performance of Cationic Block Copolymer Polyplexes
AU - Nikita A. Kozyrev
AU - Alexey V. Doroshchenko
AU - Anna D. Lapanik
AU - Natalia L. Klyachko
AU - Anton V. Lopukhov
PY - 2026
DA - 2026/10/28
JO - Polymers
DO - 10.3390/polym18212671
UR - https://www.mdpi.com/2073-4360/18/21/2671
AB - The development of efficient and biocompatible polymeric vectors remains a cornerstone of successful gene therapy. In this study, we developed a versatile polymeric platform for nucleic acid delivery by synthesizing a series of cationic block copolymers based on polyaspartamide or polyglutamide backbones and polyethylene glycol (PEG) segments. Block copolymer precursors were synthesized via ring-opening polymerization. The degrees of polymerization were confirmed via 1H NMR spectroscopy, followed by functionalization with diethylenetriamine, spermine, or spermidine. Cytotoxicity was evaluated using the WST-1 assay in HEK293 and SH-SY5Y cells. Cytotoxicity profiling identified N3-PEG114-b-pAsp(DET)62 as the least cytotoxic polymer among the tested derivatives in both cell lines. The polyplexes enhanced reporter gene expression compared with naked plasmid DNA, and an N/P ratio of 15 was selected for subsequent comparative experiments. In SH-SY5Y neuroblastoma cells, the material obtained following the dopamine-modification procedure exhibited a 1.78-fold increase in reporter fluorescence and a 1.75-fold increase in the percentage of GFP-positive cells compared with the corresponding unmodified formulation. These findings establish the engineered block copolymers as highly adaptable, low-toxicity, and efficient candidates for targeted nucleic acid delivery and support the potential of dopamine functionalization for enhancing delivery to dopamine-receptor-expressing cells.
SN - 2073-4360
ER -