Abstract

Transfection of functional genetic molecules into neuroma cells to efficiently manipulate gene expression is of great significance in neuro-associated gene therapy. However, most of the current neuroma cell gene carriers are based on viruses, which often suffer from inherent immunogenicity, carcinogenicity, and insertional mutagenesis. Here, a pH-sensitive linear poly(ortho ester) polycation (POP) with a uniform distribution of tertiary amine and hydroxyl groups is prepared by ring-opening polymerization between 4,4′-(oxybis(methylene))bis(2-methoxy-1,3-dioxolane) (OEDe) and piperazine. The prepared POP/DNA nano-assemblies show good stability and ultrasensitively controlled DNA release. Significantly, this linear polymer exhibits good biocompatibility and highly specified transfection efficiency (∼80%) on human neuroblastoma cells (SH-SY5Y), which is also serum-tolerant and exhibits deeper transfection depth. Besides, the non-responsive poly(ethylene glycol) diglycidyl ether (EGDE) polycation (PEP) is set as a control, fully demonstrating that the gene carrier POP has great potential in neuroma therapy.

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