■顺铂(CSP)是一种有效的抗癌药物,广泛用于治疗多形性胶质母细胞瘤(GBM)。然而,CSP在GBM中的临床疗效与低治疗比例相比,毒性,多药耐药(MDR)。因此,我们开发了一种通过负载顺铂的聚合物纳米平台(CSP-NP)在GBM中主动靶向顺铂的系统。
■CSP-NP通过改进的双乳液和纳米沉淀技术制备。CSP-NP的物理化学表征使用zetasizer进行,扫描电子显微镜(SEM),药物释放动力学,和药物含量分析。细胞毒性,诱导凋亡,和细胞周期特异性的CSP-NP在人GBM细胞系中的活性通过MTT法进行评估,荧光显微镜,和流式细胞术。通过荧光成像和流式细胞术测量细胞内药物摄取。通过基于流式细胞术的药物外排测定来评估CSP-NP抑制MDR转运蛋白的潜力。
■CSP-NP具有光滑的表面特性,具有离散的粒径以及所需的zeta电位,多分散指数,药物包封效率,和药物含量。CSP-NP已显示出“初始爆发效应”,随后具有持续的药物释放特性。CSP-NP在人GBM细胞中赋予剂量和时间依赖性细胞毒性并触发凋亡。有趣的是,CSP-NP显着增加摄取,内化,和抗癌药物的积累。此外,CSP-NP显著逆转人GBM细胞中的MDR转运蛋白(ABCB1和ABCG2)。
■顺铂的纳米颗粒系统似乎具有积极靶向顺铂的潜力,可作为人类GBM的有效和特异性治疗剂,从而消除了目前化疗的局限性。
UNASSIGNED: Cisplatin (CSP) is a potent anticancer drug widely used in treating glioblastoma multiforme (GBM). However, CSP\'s clinical efficacy in GBM contrasted with low therapeutic ratio, toxicity, and multidrug resistance (MDR). Therefore, we have developed a system for the active targeting of cisplatin in GBM via cisplatin loaded polymeric nanoplatforms (CSP-NPs).
UNASSIGNED: CSP-NPs were prepared by modified double emulsion and nanoprecipitation techniques. The physiochemical characterizations of CSP-NPs were performed using zeta sizer, scanning electron microscopy (SEM), drug release kinetics, and drug content analysis. Cytotoxicity, induction of apoptosis, and cell cycle-specific activity of CSP-NPs in human GBM cell lines were evaluated by MTT assay, fluorescent microscopy, and flow cytometry. Intracellular drug uptake was gauged by fluorescent imaging and flow cytometry. The potential of CSP-NPs to inhibit MDR transporters were assessed by flow cytometry-based drug efflux assays.
UNASSIGNED: CSP-NPs have smooth surface properties with discrete particle size with required zeta potential, polydispersity index, drug entrapment efficiency, and drug content. CSP-NPs has demonstrated an \'initial burst effect\' followed by sustained drug release properties. CSP-NPs imparted dose and time-dependent cytotoxicity and triggered apoptosis in human GBM cells. Interestingly, CSP-NPs significantly increased uptake, internalization, and accumulations of anticancer drugs. Moreover, CSP-NPs significantly reversed the MDR transporters (ABCB1 and ABCG2) in human GBM cells.
UNASSIGNED: The nanoparticulate system of cisplatin seems to has a promising potential for active targeting of cisplatin as an effective and specific therapeutic for human GBM, thus eliminating current chemotherapy\'s limitations.