A dual-functional buformin-mimicking poly(amido amine) for efficient and safe gene delivery
A dual-functional buformin-mimicking poly(amido amine) for efficient and safe gene delivery
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一种双功能模拟丁双胍聚（酰胺基胺），用于高效、安全的基因传递
DOI：
10.1080/1061186x.2020.1729770
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发表时间：
2020-04
影响因子：
4.5
通讯作者：
Ding Pingtian
中科院分区：
文献类型：
--
作者：
Lu Mei;Xing Haonan;Cheng Lin;Liu Hui;Lang Lang;Yang Tianzhi;Zhao Xiaoyun;Xu Hui;Ding Pingtian
Biguanides (i.e. metformin, phenformin and buformin) are antidiabetic drugs with potential antitumor effects. Herein, a polycationic polymer, N,N '-bis(cystamine)acrylamide-buformin (CBA-Bu), containing multiple biodegradable disulphide bonds and buformin-mimicking side chains was synthesised. CBA-Bu was equipped with high efficiency and safety profile for gene delivery, meanwhile exhibiting potential antitumor efficacy. As a gene vector, CBA-Bu was able to condense plasmid DNA (pDNA) into nano-sized (30 mV) uniform polyplexes that were well resistant to heparin and DNase I. Due to the reduction responsiveness of the disulphide bonds, CBA-Bu/pDNA polyplexes could release the loaded pDNA in the presence of dithiothreitol, and induce extremely low cytotoxicity in NIH/3T3 and U87 MG cells. The transfection results showed that CBA-Bu had a cellular uptake efficiency comparable to 25 kDa PEI, while a significantly higher gene expression level. Additionally, CBA-Bu had a lower IC50 value than its non-biguanide counterpart in two cancer cell lines. Furthermore, CBA-Bu could activate AMPK and inhibit mTOR pathways in U87 MG cells, a mechanism involved in the antitumor effect of biguanides. Taken together, CBA-Bu represented an advanced gene vector combining desirable gene delivery capability with potential antitumor activity, which was promising to achieve enhanced therapeutic efficacy in antitumor gene therapy.
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DOI：
10.1186/s13046-017-0498-0
发表时间：
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期刊：
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