紫杉醇纳米复合物体内体外抗宫颈癌活性评价

In vitro and in vivo evaluations of antitumor activity against cervical cancer of paclitaxel-loaded nanoparticals

目的利用二硫键共价链接紫杉醇(paclitaxel,PTX)与荧光介孔二氧化硅纳米粒(fluorescent mesoporous silica nanoparticles,FMSN),形成一种可控药物投递系统(controlled drug delivery system,CDDS),并用体内体外实验评价其抗宫颈癌活性。方法HeLa细胞分别与PTX、PTX-FMSN和空白对照共培养。细胞IQ工作站和流式细胞仪检测细胞的生长和凋亡情况。血检和组织病理学研究评价药物抗肿瘤作用和毒性作用及不良反应。结果体外研究表明,PTX-FMSN与PTX溶液相比,对HeLa细胞具有相似的抑制细胞增殖和促凋亡作用。经PTX和PTX-FMSN治疗的荷瘤裸鼠,HeLa细胞坏死率并无明显差异,但在相同剂量下,PTX-FMSN的毒性作用及不良反应明显小于PTX。结论由于毒性作用及不良反应的降低,这种氧化还原性CDDS具有被应用于宫颈癌临床治疗的美好前景。

Objective A controlled drug delivery system (CDDS) based on fluorescent mesoporous silica nanoparticles (FMSN) covalently linked paclitaxel (PTX) via disulfide linkage was prepared,in order to evaluate its efficacy of antitumor activity against cervical cancer in vitro and in vivo. Methods HeLa cells were cultured and raised with PTX,PTX-FMSN and blank control separately.The cell-IQ and flow cytometry were used to detect cell growth and apoptosis.Blood test and histopathological sections were evaluated for drug anti-tumor efficacy,toxic effects and side effects. Results In vitro studies suggested that PTX-FMSN showed similar cellular proliferation inhibition and pro-apoptotic effects against HeLa cells with PTX solution.Necrosis rates of HeLa cells were not different between PTX and PTX-FMSN treated mice,but the toxic and side effects of PTX-FMSN were significantly less than PTX under the same dose. Conclusions This redox-responsive CDDS could be potentially applied to the clinical treatment of cervical cancer due to lower toxic and side effects.