Synthesis of PEGylated cationic curdlan derivatives with enhanced biocompatibility
| Autor: | Xiang Yu, Mingming Bao, Hai Xiao, Muqier Muqier, Qingming Bao, Yifeng Li, Huricha Baigude, Shuqin Han |
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| Rok vydání: | 2021 |
| Předmět: |
beta-Glucans
Biocompatibility Chemistry Biomedical Engineering Biophysics Cationic polymerization Bioengineering Transfection Curdlan Polyethylene Glycols Biomaterials Mice chemistry.chemical_compound Biochemistry In vivo Cations Nucleic acid PEGylation Animals Nanoparticles RNA Small Interfering Cytotoxicity |
| Zdroj: | Journal of Biomaterials Science, Polymer Edition. 33:465-480 |
| ISSN: | 1568-5624 0920-5063 |
| Popis: | Cationic polysaccharides have shown excellent ability of nucleic acids delivery. However, cationic curdlan derivatives with high degree of amination cause damage to the cell membrane and induce considerable cytotoxicity, limiting their in vivo application. Herein, we synthesized PEGylated 6-amino-6-deoxy-curdlan derivatives containing cleavable disulfide bonds. The resulting polymers (denote 6AC-2S PEGx) not only showed high affinity to siRNA but also exhibited significantly decreased cytotoxicity and hemolysis effect, while showing remarkable in vitro transfection efficiency. In vivo study demonstrated that 6AC-2S PEG40, which had a lower LD50 value than that of 6AC-100, did not cause liver damage, as the i.v. injection of 6AC-2S PEG40 to mouse did not increase serum level of ALT/AST. Furthermore, tissue distribution results showed that 6AC-2S PEG40 successfully delivered siRNA to liver, lung and spleen. Collectively, our data confirmed that PEGylation can increase the biocompatibility of cationic curdlan derivatives, which is a promising carrier for nucleic acid therapeutics. |
| Databáze: | OpenAIRE |
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