拟Smac合成肽羧甲基壳聚糖磁性纳米复合物的制备及体外抗肿瘤性能研究  

The preparation and antineoplastic activity in vitro of Smac-mimic peptide-loaded O-carboxylmethylated chitosan magnetic nanoparticles

作　　者：王竞[1] 曾甫清[2] 汪良[2] 蒋国松[2] 黄慧[1] 汪涛[1] 潘晖[1] 

机构地区：[1]长江大学附属第一医院泌尿外科,湖北省荆州市434000 [2]华中科技大学同济医学院附属协和医院泌尿外科,武汉市430030

出　　处：《实用医学杂志》2012年第19期3170-3173,共4页The Journal of Practical Medicine

基　　金：教育部博士学科点专项科研基金课题(编号:20060487066)

摘　　要：目的:探讨拟Smac合成肽羧甲基壳聚糖磁性纳米复合物的制备及联合恒定外磁场体外对膀胱癌细胞的凋亡促进作用。方法:以羧甲基壳聚糖为骨架与具有超顺磁性的Fe3O4纳米粒合成纳米载体粒子,将拟Smac合成肽SmacN7与其结合,制备拟Smac合成肽羧甲基壳聚糖磁性纳米复合物,并通过透射电镜、振动样磁强计等考察其理化性质;Hoechst33258染色观察外加磁场下纳米复合物诱导膀胱癌T24细胞凋亡的形态,MTT比色分析法观察其对肿瘤细胞的生长抑制作用。结果:拟Smac合成肽羧甲基壳聚糖磁性纳米粒子的粒径约为46.2nm;磁化曲线提示具有超顺磁性;载药量和包封率分别为(31.8±3.6)%和(65.2±2.4)%并具有良好的药物控释性能;外加磁场下磁性纳米粒子能使肿瘤细胞呈现明显的凋亡形态改变并表现出显著的生长抑制活性。结论:拟Smac合成肽羧甲基壳聚糖磁性纳米复合物具有粒径小、较强的磁响应性、载药量和包封率高和良好的药物缓释性能,联合恒定外磁场具有明显的促进肿瘤细胞凋亡的作用,为膀胱肿瘤的生物治疗提供了新的切入点。Objective To prepare Smac-mimic peptide-loaded O-carboxylmethylated chitosan （O-CMC） magnetic nanoparticles （SmacN7-O-CMC-MNPs）, and to investigate its effects on the apoptosis of bladder carcinoma T24 cells in vitro when combined with constant external magnetic fields. Methods The magnetic SmacN7-O-CMC- MNPs was composed by O-CMC, SmacN7, and Fe304 nanoparticles. And its physicochemical characteristics were confirmed by TEM and vibrating sample magnetometer. The apoptosis of bladder carcinoma T24 cells was observed by Hoechst33258 staining and the inhibition rates （IR） was assayed by MTY when SmacN7-O-CMC-MNPs was combined with constant external magnetic fields. Results The mean diameter of SmacN7-O-CMC-MNPs was 46.2 nm with round shape and the loading dose and trapping efficiency was （31.8±3.6）% and （65.2±2.4）%, respectively. Magnetization curve showed superparamagnetism. SmacN%O-CMC-MNPs nanoparticles could apparently induce apoptotic appearance and inhibit the growth of bladder cancer cells when combined with constant external magnetic fields. Conclusion SmacN7-O-CMC-MNPs had small particle size, good magnetic responsiveness, high loading rate and embedding ratio. It can sharply promote apoptosis of bladder cancer cells when combined with constant external magnetic fields and implies a promising future for the biological therapy for bladder cancer.

关 键 词：纳米粒子 SMAC 合成肽 O-羧甲基壳聚糖 凋亡 

分 类 号：R318.08[医药卫生—生物医学工程]