Tian Yong, Yin Haitao, Xu Huae
Department of Radiotherapy, the Central Hospital of Xuzhou, Affiliated Hospital of Southeast University, Xuzhou, China.
Department of Pharmacy, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Curr Drug Deliv. 2016;13(6):946-52. doi: 10.2174/1567201813666160303104439.
Tetrandrine (Tet), a kind of herbal medicine belonging to the family of bis-benzylisoquinoline alkaloid, has gained more attraction for its potential anti-tumor effects. However, its potential utilization in clinic is greatly hampered by the poor pharmacokinetcs profile due to its insolubility. Recently, biodegradable polymeric nanoparticles with amphilic copolymers as drug carriers have shown better bioavailability against tumor as promising tumor-targeted drug delivery system.
In the current study, Tet-loaded nanoparticles (Tet-NPs) was prepared with amphiphilic block copolymer as drug carriers. The physiochemical characterization, in vitro and in vivo antitumor effect of nanoparticles were evaluated.
In vitro study demonstrated the superior cell inhibitory effect of Tet-NPs. Most importantly, the viability of cells exposed to Tet-NPs was significant lower than that of cells treated with free Tet at lower equivalent doses. Moreover, Tet- NPs induced apoptosis and inhibited the proliferation of cells more effectively than free did at the equivalent concentration. Western blot showed that the expression of anti-apoptotic protein Bcl-2, Bcl-XL was significantly promoted while the pro-apoptotic Bax was significantly inhibited by the treatment of Tet-NPs.
Data from the current study suggested that Tet-NPs is a promising delivery nano-system for the treatment of osteosarcoma.
粉防己碱(Tet)是一种双苄基异喹啉生物碱类草药,因其潜在的抗肿瘤作用而备受关注。然而,由于其不溶性导致的不良药代动力学特性,极大地阻碍了其在临床上的潜在应用。近来,以两亲性共聚物为药物载体的可生物降解聚合物纳米粒作为一种有前景的肿瘤靶向给药系统,在抗肿瘤方面显示出更好的生物利用度。
在本研究中,以两亲性嵌段共聚物为药物载体制备了载粉防己碱纳米粒(Tet-NPs)。对纳米粒的理化性质、体外和体内抗肿瘤作用进行了评价。
体外研究表明Tet-NPs具有优异的细胞抑制作用。最重要的是,在较低等效剂量下,暴露于Tet-NPs的细胞活力显著低于游离粉防己碱处理的细胞。此外,在等效浓度下,Tet-NPs比游离粉防己碱更有效地诱导细胞凋亡并抑制细胞增殖。蛋白质免疫印迹法显示,Tet-NPs处理显著促进抗凋亡蛋白Bcl-2、Bcl-XL的表达,同时显著抑制促凋亡蛋白Bax的表达。
本研究数据表明,Tet-NPs是一种有前景的用于治疗骨肉瘤的递送纳米系统。