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Colloids Surf B Biointerfaces. 2015 Dec 1;136:1148-55. doi: 10.1016/j.colsurfb.2015.11.015. Epub 2015 Nov 21.

Nucleobase-modified dendrimers as nonviral vectors for efficient and low cytotoxic gene delivery.

Author information

1
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, People's Republic of China.
2
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
3
East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, People's Republic of China.
4
East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, People's Republic of China. Electronic address: yycheng@mail.ustc.edu.cn.
5
Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China. Electronic address: jianruxiao@163.com.

Abstract

Cationic dendrimers are associated with relatively low transfection efficacy and high toxicity in gene delivery. Surface modification of these dendrimers with functional ligands may resolve these issues. Here, we proposed a novel strategy to prepare surface-engineered dendrimers with high transfection efficacy and low toxicity on transfected cells. Several nucleobase analogues were modified on cationic dendrimers by a facile method. These nucleobase-modified dendrimers show improved transfection efficacy and reduced cytotoxicity compared to unmodified dendrimers on HEK293 and HeLa cells. Efficacy of the most efficient polymer is comparable to that of commercial transfection reagents such as SuperFect, PolyFect, and Lipofectamine 2000. The improved transfection efficacy of dendrimers after nucleobase modification is probably attributed to easier intracellular DNA unpacking and lower cytotoxicity. The results provide a valuable insight to guide the design of efficient and low cytotoxic gene vectors.

KEYWORDS:

Dendrimer; Gene delivery; Nucleobase; Polymer; Surface modification

PMID:
26613860
DOI:
10.1016/j.colsurfb.2015.11.015
[Indexed for MEDLINE]

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