4.7 Article

pH-Sensitive Cationic Polymer/DNA Nano-assemblies for Efficient Gene Transfection in Neuroma Cells

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ACS APPLIED NANO MATERIALS
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AMER CHEMICAL SOC
DOI: 10.1021/acsanm.3c01520

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gene therapy; transfection efficiency; orthoester; neuroma cell; transfection depth

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In this study, a pH-sensitive linear poly(ortho ester) polycation was successfully prepared and used for gene transfection in neuroma cells. The polymer showed good biocompatibility and highly specified transfection efficiency on human neuroblastoma cells, with serum tolerance and deeper transfection depth. Compared with the control group, this polymer demonstrated great potential in neuroma therapy.
Transfectionof functional genetic molecules into neuroma cellsto efficiently manipulate gene expression is of great significancein neuro-associated gene therapy. However, most of the current neuromacell gene carriers are based on viruses, which often suffer from inherentimmunogenicity, carcinogenicity, and insertional mutagenesis. Here,a pH-sensitive linear poly(ortho ester) polycation (POP) with a uniformdistribution of tertiary amine and hydroxyl groups is prepared byring-opening polymerization between 4,4 '-(oxybis(methylene))bis(2-methoxy-1,3-dioxolane)(OEDe) and piperazine. The prepared POP/DNA nano-assemblies show goodstability and ultrasensitively controlled DNA release. Significantly,this linear polymer exhibits good biocompatibility and highly specifiedtransfection efficiency (similar to 80%) on human neuroblastoma cells(SH-SY5Y), which is also serum-tolerant and exhibits deeper transfectiondepth. Besides, the non-responsive poly(ethylene glycol) diglycidylether (EGDE) polycation (PEP) is set as a control, fully demonstratingthat the gene carrier POP has great potential in neuroma therapy.

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