聚乙二醇-聚(乳酸-碳酸酯)-紫杉醇纳米胶束对SKOV3卵巢癌的抑制作用

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

INHIBITION OF SKOV3 OVARIAN CANCER BY NANOMICELLES CONSTRUCTED FROM POLY(ETHYLENE GLYCOL)-b-POLY (LACTIDE-co-CARBONATE/PACLITAXEL) CONJUGATES

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 nm,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 9th 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