Construction of serum-resistant cationic polymer α-CD-PAMAM and evaluation of its performances as gene delivery vector
10.16438/j.0513-4870.2016-0781
- VernacularTitle:α-CD-PAMAM抗血清阳离子聚合物的构建及其作为基因载体的性能评价
- Author:
Ling-hao QIN
1
;
Duan-wen CAO
1
;
Shi-rong PAN
2
;
Jian-hai CHEN
1
Author Information
1. Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
2. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
cyclodextrin;
polyamidoamine;
serum-resistance;
gene delivery vector
- From:
Acta Pharmaceutica Sinica
2017;52(1):139-145
- CountryChina
- Language:Chinese
-
Abstract:
Polyamidoamine (PAMAM) dendrimers as synthetic gene vectors are efficient gene delivery systems. In this study, a kind of α-cyclodextrin-PAMAM conjugates polymer (CyD-G1) was synthesized as a gene delivery vector. Based on 1H NMR detectation, about 6.4 PAMAM-G1 molecules was grafted onto an α-CD core. Agarose gel electrophoresis revealed that CyD-G1 could efficiently bind with DNA to condense them into nano-scale particles, which showed a similar binding capacity of PEI-25K. Besides, it could protect DNA from DNase I degradation in a low N/P ratio. When N/P ratio in the CyD-G1/DNA polyplex was 40, the average particle size of CyD-G1/DNA polyplex was about 120 nm, and zeta potential was +21 mV. This polyplex could maintain its particle size in serum-containing solution within 360 min. In comparison with PEI-25K carrier, CyD-G1 showed low cytotoxicity in various cell lines. Cell transfection results showed that CyD-G1 efficiently delivered DNA into cells at N/P=80 compared with Lipofectamine 2000 and PEI-25K.Unlike Lipofectamine 2000 and PEI-25K, in serum-containing test condition, CyD-G1/DNA polyplex could maintain the transgene activities. The results of confocal laser scanning microscopy indicated that most DNA entered into cell nuclei within 4 h, and this phenomenon was consistent with the results calculated by flow cytometry. Taken together, CyD-G1 showed good transgene activities and the gene delivery vector could be used not only in vitro but also in vivo.
