Linear-branched poly(β-amino esters)/DNA nano-polyplexes for effective gene transfection and neural stem cell differentiation.

Yuheng Cao, Haobo He, Kaili Cao, Yongyang Liu, Dehua Huang, Tuanwei Li, Guangcun Chen

Biomedical materials (Bristol, England) 2022 Feb 07

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Controllable regulation of stem cell differentiation is a critical concern in stem cell-based regenerative medicine. In particular, there are still great challenges in controlling the directional differentiation of neural stem cells (NSCs) into neurons. Herein, we developed a novel linear-branched poly(β-amino esters) (S4-TMPTA-BDA-DT, STBD) through a two-step reaction. The synthesized linear-branched polymers possess multiple positively charged amine terminus and degradable intermolecular ester bonds, thus endowing them with excellent properties such as high gene load, efficient gene delivery, and effective gene release and transcription in cells. In the mCherry transfection test, a high transfection efficiency of approximately 70% was achieved in primary NSCs after a single transfection. Moreover, STBD also showed high biocompatibility to NSCs without disturbing their viability and neural differentiation. With the high gene delivery property, STBD is capable of delivering siRNA (shSOX9) expression plasmid into NSCs to significantly interfere with the expression of SOX9, thus enhancing the neuronal differentiation and maturation of NSCs. The STBD/DNA nano-polyplex represents a powerful non-viral approach of gene delivery for manipulating the differentiation of stem cells, showing broad application prospects in NSC-based regenerative therapy for treating neurodegenerative diseases. © 2022 IOP Publishing Ltd.

Citation

Yuheng Cao, Haobo He, Kaili Cao, Yongyang Liu, Dehua Huang, Tuanwei Li, Guangcun Chen. Linear-branched poly(β-amino esters)/DNA nano-polyplexes for effective gene transfection and neural stem cell differentiation. Biomedical materials (Bristol, England). 2022 Feb 07;17(2)