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Photo-Triggered Delivery of siRNA and Paclitaxel into Breast Cancer Cells Using Catanionic Vesicles
ACS Applied Bio Materials ( IF 4.7 ) Pub Date : 2020-10-19 , DOI: 10.1021/acsabm.0c00503
Zumra Peksaglam Seidel 1 , Xiaoyang Zhang 1 , Melanie A MacMullan 1 , Nicholas Alexander Graham 1 , Pin Wang 1 , C Ted Lee 1
Affiliation  

Localized drug delivery holds great promise as a means of circumventing traditional chemotherapy side effects associated with high toxicity and prolonged treatments. Nanosized carriers (i.e., with diameters <100 nm) can often accumulate in tumor cells, yet it remains a challenge to design such carriers that are at the same time durable (to survive delivery) and degradable (to release the payload once inside cells). In the present study, photoresponsive catanionic vesicles are utilized to codeliver Bcl-2 siRNA and paclitaxel into MDA-MB-231 human breast cancer cells. These vesicles, which form spontaneously upon simple mixing of an azobenzene-based cationic surfactant and a conventional anionic surfactant, disassociate into free surfactants upon UV illumination. This allows for phototriggered release of the coloaded therapeutics following cellular uptake, which is shown to enhance both cell death and protein suppression. Dynamic light scattering, zeta potential, small-angle neutron scattering, and fluorescence spectroscopy measurements are utilized to determine the optimal vesicle size, charge, bilayer thickness, and concentration for encapsulation and uptake. Cell viability, flow cytometry, and confocal microscopy are used to demonstrate safe and effective dosages, whereas knockdown of Bcl-2 protein expression was confirmed by Western blots.

中文翻译:

使用阳离子囊泡将 siRNA 和紫杉醇光触发递送至乳腺癌细胞

作为规避与高毒性和长期治疗相关的传统化疗副作用的一种手段,局部给药具有很大的前景。纳米级载体(即直径<100 nm)通常​​可以在肿瘤细胞中积累,但设计这样的载体仍然是一个挑战,既耐用(在递送过程中存活)又可降解(一旦进入细胞就释放有效载荷) . 在本研究中,光响应性阳离子囊泡用于将 Bcl-2 siRNA 和紫杉醇共递送到 MDA-MB-231 人乳腺癌细胞中。这些囊泡在基于偶氮苯的阳离子表面活性剂和常规阴离子表面活性剂的简单混合时自发形成,在紫外线照射下解离成游离的表面活性剂。这允许在细胞摄取后光触发释放共同加载的治疗剂,这被证明可以增强细胞死亡和蛋白质抑制。动态光散射、zeta 电位、小角中子散射和荧光光谱测量用于确定最佳囊泡大小、电荷、双层厚度以及封装和吸收的浓度。细胞活力、流式细胞术和共聚焦显微镜用于证明安全有效的剂量,而蛋白质印迹证实了 Bcl-2 蛋白表达的敲低。双层厚度,以及封装和吸收的浓度。细胞活力、流式细胞术和共聚焦显微镜用于证明安全有效的剂量,而蛋白质印迹证实了 Bcl-2 蛋白表达的敲低。双层厚度,以及封装和吸收的浓度。细胞活力、流式细胞术和共聚焦显微镜用于证明安全有效的剂量,而蛋白质印迹证实了 Bcl-2 蛋白表达的敲低。
更新日期:2020-11-16
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