A Tf-modified tripterine-loaded coix seed oil microemulsion enhances anti-cervical cancer treatment
A Tf-modified tripterine-loaded coix seed oil microemulsion enhances anti-cervical cancer treatment
复制标题
Tf修饰雷公藤红素薏苡仁油微乳增强抗宫颈癌治疗
DOI：
10.2147/ijn.s182475
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发表时间：
2018-01-01
影响因子：
8
通讯作者：
Chen, Yan
中科院分区：
文献类型：
--
作者：
Chen, Yunyan;Qu, Ding;Chen, Yan
目的制备转铁蛋白修饰的薏苡仁油雷公藤红素微乳（Tf-CT-MEs），以提高肿瘤特异性蓄积和渗透，增强对宫颈癌的治疗效果。材料与方法采用一步乳化法制备载雷公藤红素的薏苡仁油微乳。通过透射电子显微镜和动态光散射检测CT-ME和Tf-CT-ME的形态、尺寸和zeta电位。采用流式细胞仪研究HeLa细胞对药物的摄取及其机制。使用HeLa三维（3D）肿瘤球体作为模型研究肿瘤内渗透。MTT法检测CT-ME和Tf-CT-ME对HeLa细胞的细胞毒性。此外，还检测了CT-ME和Tf-CT-ME诱导HeLa细胞凋亡的凋亡率。结果薏苡仁油和CT-ME的粒径较小（32.47±0.15 nm），表面电荷接近中性（−0.36±0.11 mV）。转铁蛋白修饰后，Tf-CT-MEs的粒径略有增加，为40.02±0.21 nm，但zeta电位显著降低，为-13.63 ± 1.31 mV。Tf-CT-ME对HeLa细胞的IC 50为0.7260 µM，比CT-ME低2.58倍。在细胞研究中，异硫氰酸荧光素（FITC）标记的Tf-CT-MEs（FITC/Tf-CT-MEs）的细胞内荧光强度比FITC标记的CT-MEs（FITC/CT-MEs）高2.28倍。在3D肿瘤球体表面下方350 µm处观察到Tf-CT-ME的荧光信号。用Tf-CT-MEs处理的细胞的凋亡率分别是用CT-MEs和雷公藤红素处理的细胞的1.73倍和2.77倍，这与雷公藤红素的尿道靶向递送有关。此外，Tf-CT-MEs能够显著下调细胞抗凋亡蛋白的水平，并将细胞增殖阻滞在G2/M期。结论Tf-CT-MEs有望成为宫颈癌联合治疗的有效药物载体。
Purpose A transferrin-modified microemulsion carrying coix seed oil and tripterine (Tf-CT-MEs) was developed for improved tumor-specific accumulation and penetration to enhance cervical cancer treatment. Materials and methods Tripterine-loaded coix seed oil microemulsion (CT-MEs) was prepared through one-step emulsion method. The morphology, size, and zeta potential of CT-MEs and Tf-CT-MEs were examined by transmission electron microscopy and dynamic light scattering. The cellular uptake and mechanisms of HeLa cells were investigated by flow cytometry. Intratumor penetration was investigated using a HeLa three-dimensional (3D) tumor spheroid as the model. The cytotoxicity of the CT-MEs and Tf-CT-MEs against HeLa cells were evaluated by the MTT assay. Additionally, the apoptotic rate of CT-MEs and Tf-CT-MEs inducing apoptosis in HeLa cells was evaluated. Results In the physicochemical characterization, coix seed oil and CT-MEs exhibited a small size (32.47±0.15 nm) and nearly neutral surface charge (−0.36±0.11 mV). After modification with transferrin, the particle size of Tf-CT-MEs slightly increased to 40.02±0.21 nm, but the zeta potential decreased remarkably to -13.63±1.31 mV. The IC50 of Tf-CT-MEs against HeLa cells was 0.7260 µM, which was 2.58-fold lower than that of CT-MEs. In cellular studies, the intracellular fluorescence intensity of fluorescein isothiocyanate (FITC)-labeled Tf-CT-MEs (FITC/Tf-CT-MEs) was 2.28-fold higher than that of FITC-labeled CT-MEs (FITC/CT-MEs). The fluorescence signal of Tf-CT-MEs was observed at 350 µm below the surface of the 3D tumor spheroid. The apoptotic rate of cells treated with Tf-CT-MEs was 1.73- and 2.77-fold higher than that of cells treated with CT-MEs and tripterine, respectively, which was associated with mitochondrial-targeted delivery of tripterine. Moreover, Tf-CT-MEs was capable of significantly downregulating the cellular level of antiapoptotic proteins and arrested cell proliferation in the G2/M phase. Conclusion Taken together, Tf-CT-MEs holds promising potential to be an efficient drug delivery system for combinational therapy of cervical cancer.