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| Content Provider | Royal Society of Chemistry (RSC) |
|---|---|
| Author | Li, Yongyong Yue, Dong Shi, Donglu Li, Shuo Yi, Qiangying Gu, Zhongwu Cai, Xiaojun |
| Copyright Year | 2015 |
| Abstract | Gene carriers made from polylysine are of interest in relation to gene therapy but suffer from the lack of transfection efficiency due to limited stability and endosomal escape ability. To address this problem, we designed and developed Schiff-base linked imidazole modified polylysine with a reversible-PEGylation catiomer (SL-ImPEG-SS-PLL) for high efficiency gene delivery. The reversible PEGylation was introduced for in vivo circulation, as well as selective PEG detachment to augment the cellular internalization, while introducing Schiff-base linked imidazole residues into polylysine was expected to accelerate the endosomal escape of the DNA payload, as well as facilitate intracellular DNA unpacking and release, thus significantly enhancing gene delivery efficiency. The size alteration of the SL-I15mPEG-SS-PLL/pDNA polyplexes in the presence of 10 mM GSH suggests stimulus-induced PEG detachment under tumor relevant reduction conditions. Acid–base titration assays indicate that imidazole residues confer on polylysine remarkable buffering ability. The agarose gel retardation assay suggests that the Schiff-base linkages provide an increased DNA binding ability to protect DNA against nucleases and timely intracellular DNA unpacking to permit DNA dissociation from polylysine and access to transcriptional machinery. Biological efficacy assessment of this multifunctional carrier, using pEGFP and pGL-3 as reporter genes, indicates comparable to or even higher transfection efficiencies than gold standard PEI and their transfection efficiencies are slightly affected by serum. More importantly, in vivo transfection of pEGFP reveals that GFP expression was found not only in some of the important organs, such as the liver, spleen, kidneys and lungs, but also in the transplanted carcinoma. These experimental results suggest that the reversible PEGylation and Schiff-base linked imidazole modification make SL-ImPEG-SS-PLL a great potential candidate for an effective and biocompatible gene delivery system. |
| Starting Page | 1507 |
| Ending Page | 1517 |
| Page Count | 11 |
| File Format | HTM / HTML PDF |
| ISSN | 2050750X |
| Volume Number | 3 |
| Issue Number | 8 |
| Journal | Journal of Materials Chemistry B |
| DOI | 10.1039/c4tb01724b |
| Language | English |
| Publisher | Royal Society of Chemistry |
| Access Restriction | Open |
| Subject Keyword | Gene Polylysine Gene therapy Transfection Imidazole PEGylation DNA Acid\u2013base titration Agarose Dissociative Reporter gene Gold standard Green fluorescent protein Liver Spleen Carcinoma Biocompatibility |
| Content Type | Text |
| Resource Type | Article |
| Subject | Chemistry Medicine Materials Science Biomedical Engineering |
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