细胞内转运载体超支化聚砜胺及其生物相容性  

Biocompatibility and Biodistribution of a Novel Cationic Polymer——Hyperbranched Poly(sulfone-amine) as an Intracellular Delivery System

作　　者：陈素芸[1] 孙国明[2] 姜磊[1] 李楠[1] 李培勇[1] 朱新远[2] 

机构地区：[1]上海交通大学医学院附属瑞金医院核医学科,上海200025 [2]上海交通大学化学化工学院,上海200240

出　　处：《高等学校化学学报》2009年第4期825-829,共5页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:20574044,50633010,50773037);新世纪优秀人才计划;上海市重点学科医学影像学与核医学资助

摘　　要：通过制备超支化聚砜胺-异硫氰酸荧光素聚合物(PSA-FITC),研究其生物相容性、肿瘤细胞对其内吞作用和在正常小鼠体内的生物分布,以探讨PSA作为载体进行药物和基因体内输送的可行性.在碱性条件下共价结合PSA与FITC,形成荧光标记聚合物(PSA-FITC)后测定聚合物中FITC含量.在不同时间点,通过流式细胞术检测细胞对聚合物的内吞作用;正常balb/c裸鼠尾静脉注射PSA-FITC 24 h后,用小动物活体荧光成像系统研究各脏器聚合物分布.不同浓度PSA与3T3小鼠成纤维细胞及KB人口腔上皮肿瘤细胞分别孵育24,48,72 h后,通过MTT法测得其生物相容性.结果表明,PSA生物相容性良好,72 h的细胞半抑制浓度大于1 mg/mL.细胞摄入PSA-FITC高效快速,3 h阳性细胞百分含量为99.24%±1.03%,且具有时间依赖性.在正常小鼠体内,PSA在各主要脏器或组织中无明显特异性浓聚.超支化聚砜胺具有明显生物低毒性和高效细胞内转运特点.由于其表面功能基团容易改性,作为载体,通过连接结合配体或抗体,在肿瘤的主动靶向治疗中具有广阔的应用前景.Hyperbranched poly（sulfone-amine） （PSA） is a novel class of hyperbranched macromolecule. In order to assess its feasibility of using PSA as a drug delivery system, we synthesized PSA-FITC by conjugating a fluorescent diagnostic agent fluorescein isothiocyanate （FITC） to the terminal amino groups of PSA covalently. As measured by UV-Vis spectrophotometer at 488 nm, the resulting conjugate contained 19 molecules of FITC per unit of PSA, or 0.08 molecules of FITC per repeat unit of PSA. Cellular internalization ratio of PSA were studied by flow cytometry（FACS） and demonstrated that the cellular uptake was time dependent. The in vitro biocompatibility was examined by MTT method against 3T3 cell line and showed no notable effect on bioaetivity of the cells. FITC labeled PSA was injected i.v. into normal nude mice. The optical imaging of dissected major organs/tissues revealed that preferential accumulation in specific organs was not observed at 24 h postinjection. The results suggest that PSA has characteristics of good biocompatibility, high efficiency of cellular uptake and modifiable surface function groups as well, which can serve as excellent platforms for a variety of therapeutic and imaging agents. It can be taken as an attractive drug/gene carrier system for intracellular delivery.

关 键 词：超支化聚砜胺 细胞毒性 细胞内转运 生物分布 生物相容性 

分 类 号：O631[理学—高分子化学]