Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 17, Pages -Publisher
MDPI
DOI: 10.3390/ijms22179606
Keywords
gene delivery; non-viral vectors; polyplex formation; polyglycidol copolymers; cationic copolymers; DNA complexation; cell internalization; cytotoxicity
Funding
- Operational Program Science and Education for Smart Growth 2014-2020
- European Union through the European Structural and Investment Funds [BG05M2OP001-1.002-0012]
- Ministry of Education and Science of the Republic of Bulgaria - National Program Innovative Low-Toxic and Biologically Active Means for Precision Medicine-BioActiveMed [01-217/30.11.2018]
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The study evaluated the potential of linear polyglycidol-based copolymers for gene therapy, demonstrating their ability to condense DNA into stable nanoparticles through electrostatic interactions. Modified copolymers showed low to moderate cytotoxicity on human cancer cell lines. Cell internalization evaluation confirmed the successful delivery of DNA into cancer cells by the polyplexes.
Gene therapy is an attractive therapeutic method for the treatment of genetic disorders for which the efficient delivery of nucleic acids into a target cell is critical. The present study is aimed at evaluating the potential of copolymers based on linear polyglycidol to act as carriers of nucleic acids. Functional copolymers with linear polyglycidol as a non-ionic hydrophilic block and a second block bearing amine hydrochloride pendant groups were prepared using previously synthesized poly(allyl glycidyl ether)-b-polyglycidol block copolymers as precursors. The amine functionalities were introduced via highly efficient radical addition of 2-aminoethanethiol hydrochloride to the alkene side groups. The modified copolymers formed loose aggregates with strongly positive surface charge in aqueous media, stabilized by the presence of dodecyl residues at the end of the copolymer structures and the hydrogen-bonding interactions in polyglycidol segments. The copolymer aggregates were able to condense DNA into stable and compact nanosized polyplex particles through electrostatic interactions. The copolymers and the corresponding polyplexes showed low to moderate cytotoxicity on a panel of human cancer cell lines. The cell internalization evaluation demonstrated the capability of the polyplexes to successfully deliver DNA into the cancer cells.
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