摘要
制备了2种两亲性生物降解嵌段共聚物聚乙二醇-聚(乳酸-碳酸酯),进而与紫杉醇和叶酸共价键合,形成高分子-紫杉醇键合物和高分子-叶酸键合物,将它们共组装成复合纳米胶束,直径约50 nm,含紫杉醇27 wt%,含叶酸1.4 wt%.培养了人卵巢癌SKOV3细胞,采用四氮唑(MTT)比色法、流式细胞术(FCM)证明了市售紫杉醇(Taxol)、紫杉醇胶束(M(PTX))及叶酸靶向紫杉醇胶束(FA-M(PTX))在10μg/mL浓度下对SKOV3细胞生长有明显抑制作用,并且M(PTX)和FA-M(PTX)优于Taxol.构建了皮下卵巢癌balb/c荷瘤裸鼠动物模型,考察了Taxol,M(PTX)和FA-M(PTX)对肿瘤生长的抑制能力.在20 mg/kg的剂量下,体外测量的肿瘤体积、9天观察的瘤体重量以及动物的生存期数据都表明,Taxol,M(PTX)和FA-M(PTX)三者都能抑制SKOV3肿瘤的生长,抑制能力的顺序为Taxol<M(PTX)<FA-M(PTX).所以,以双亲生物降解高分子为载体的键合紫杉醇纳米胶束及其靶向制剂有望用于对SKOV3卵巢癌的化疗.
Two amphiphilic biodegradable block copolymers, poly（ethylene glycol）-b-poly（lactide-co- carbonate） ,were prepared and then conjugated with paclitaxel （PTX） and folic acid （FA）, respectively, to form polymer-PTX conjugate and polymer-FA conjugate. These two conjugates were co-assembled into composite nanomicelles with an average diameter of ca. 50 am, a PTX content of 27 wt% and a FA content of 1.4 wt%. Human ovarian cancer SKOV3 cells were cultured. MTT assay and flow cytometry analysis showed that Taxol,M（PTX） and FA-M（PTX） could inhibit the growth of SKOV3 cells at a PTX concentration of 10 μg/mL, M （PTX） and FA-M （PTX） were more efficient than Taxol. Xenograft subcutaneous SKOV3 cancer models were constructed in balb/c mice. Inhibition of the tumor growth by Taxol, M （PTX） and FA＇M （PTX） was examined. At a dosage of 20 mg/kg,the tumor volume measurement,the tumor weight measurement on the 9＇h day and the survival curve all showed that Taxol, M （PTX） and FA-M （PTX） could inhibit the growth of the SKOV3 cancers, in the order of Taxol 〈 M （PTX） 〈 FA-M （PTX）. Therefore, the amphiphilic biodegradable polymer-PTX conjugate nanomicelles and the targeted formulations are expected to be used in chemotherapy of ovarian cancers.
出处
《高分子学报》
SCIE
CAS
CSCD
北大核心
2012年第8期915-922,共8页
Acta Polymerica Sinica
基金
国家自然科学基金(基金号21174143和51103148)资助项目
关键词
卵巢癌
靶向
胶束
聚乙二醇-聚(乳酸-碳酸酯)
叶酸
紫杉醇
Ovarian cancer, Targeting, Poly （ ethylene glycol）-b-poly （lactide-co-carbonate） , Folic acid,Paclitaxel
