Multifunctional Hyperbranched Glycoconjugated Polymers Based on Natural Aminoglycosides
Multifunctional Hyperbranched Glycoconjugated Polymers Based on Natural Aminoglycosides
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基于天然氨基糖苷类的多功能超支化糖共轭聚合物
DOI：
10.1021/bc300016b
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发表时间：
2012-06-01
影响因子：
4.7
通讯作者：
Sun, Jian
中科院分区：
文献类型：
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作者：
Chen, Mingsheng;Hu, Mei;Sun, Jian
以天然氨基糖苷类抗生素为原料，制备了高转染率、低细胞毒性、抗肿瘤和抗菌活性的多功能基因载体。通过庆大霉素与N，N '-亚甲基双丙烯酰胺的Michael加成聚合反应，合成了阳离子超支化糖共轭聚合物，并通过FTIR、H-1 NMR、C-13 NMR、GPC、zeta电位和酸碱滴定等方法对其理化性质进行了表征。这些超支化糖缀合聚阳离子的细胞毒性低，因为可降解的糖苷和酰胺键在酸性条件下水解。由于聚合物中存在不同的伯、仲、叔胺，超支化糖共轭聚合物表现出高缓冲能力和强的DNA缩合能力，导致高转染效率。同时，由于天然氨基糖苷类化合物的引入，所得到的超支化糖缀合聚合物有效地抑制了癌细胞和细菌的生长。基于天然氨基糖苷类的多功能超支化糖缀合物结合了基因转染、抗肿瘤和抗菌等多种功能，有望在保护肿瘤患者免受细菌感染方面发挥重要作用。
Multifunctional gene vectors with high transfection, low cytotoxicity, and good antitumor and antibacterial activities were prepared from natural aminoglycosides. Through the Michael-addition polymerization of gentamycin and N,N'-methylenebisacrylamide, cationic hyperbranched glycoconjugated polymers were synthesized, and their physical and chemical properties were analyzed by FTIR, H-1 NMR, C-13 NMR, GPC, zeta-potential, and acid base titration techniques. The cytotoxicity of these hyperbranched glycoconjugated polycations was low because of the hydrolysis of degradable glycosidic and amide linkages in acid conditions. Owing to the presence of various primary, secondary, and tertiary amines in the polymers, hyperbranched glycoconjugated polymers showed high buffering capacity and strong DNA condensation ability, resulting in the high transfection efficiency. In the meantime, due to the introduction of natural aminoglycosides into the polymeric backbone, the resultant hyperbranched glycoconjugated polymers inhibited the growth of cancer cells and bacteria efficiently. Combining the gene transfection, antitumor, and antibacterial abilities together, the multifunctional hyperbranched glycoconjugated polymers based on natural aminoglycosides may play an important role in protecting cancer patients from bacterial infections.