细胞膜仿生修饰树枝状聚酰胺-胺的研究

SURFACE ENGINEERING OF POLY (AMIDO-AMINE) via BIOMIMETIC PHOSPHORYLCHOLINE

利用2-丙烯酰氧基乙基磷酸胆碱的双键与树枝状聚酰胺-胺表面的氨基进行Michael加成反应,实现树枝状聚酰胺-胺表面的磷酸胆碱仿生修饰,修饰过程用FTIR、1H-NMR进行了表征.体外细胞活性测定和细胞形貌观察证实磷酸胆碱仿生修饰有效地改善了聚酰胺-胺树枝状聚合物的生物相容性;修饰后的聚酰胺-胺树枝状聚合物表面剩余的氨基仍然可以有效的与DNA复合,有可能作为一种潜在的基因载体得到广泛应用.

Well-defined dendrimer,poly（amido-amine） dendrimer（PAMAM）,was surface engineered via biomimetic phosphorylcholine（PC） to achieve a potential biocompatible candidate for gene delivery.PAMAM dendrimer is proven to be an efficient gene carrier itself,but it is associated with certain problems such as low water solubility and considerable cytotoxicity.PC-based polymers were designed with mimicking the biomembrane structure and widely used to improve the biocompatibility of various medical devices.Surface modification of PAMAM via phosphorylcholine is conceived to improve the biocompatibility of PAMAM.Generation 5.0 PAMAM dendrimer（G5） has been synthesized by divergent method with ethylenediamine as core.The surface of PAMAM was conjugated with PC groups via the Michael addition reaction between the 2-acryloyloxyethyl phosphorylcholine（APC） and the primary amines located on G5.After dialysis in distilled water and lyophilization,the PC modified PAMAM G5（G5-PC） was obtained.The success of the PC modification of PAMAM was followed with FTIR and 1H-NMR characterigzation.The average primary amino group numbers of the G5 and G5-PC were followed through 1H-NMR and potentiometric titration.While there were 106 primary amine groups on the native PAMAM,the surface modification of PAMAM resulted in approximately 50 PC groups on the G5-PC and 56 primary amine groups were remained.Cell viability tests and morphology observation indicated that the cytotoxicity of G5-PC was much lower in ECV304 cell lines in comparison with that of native PAMAM G5.The biomimetic PC modification sufficiently improved the biocompatibility of the native G5.The surface charges of the G5 and G5-PC were measured via zeta potential measurements,and their zeta potentials were ＋22.4 and ＋33.4 mV,respectively.The positive surface charges allowed the G5-PC to form complexes with DNA as indicated by particle size analysis.These results suggested that the biomimetic phosphorylcholine surface engineered poly（amido-amine） dendrimers could be an excellent biocompatible candidate for gene delivery systems.