Seidel Zumra Peksaglam, Zhang Xiaoyang, MacMullan Melanie A, Graham Nicholas Alexander, Wang Pin, Lee C Ted
Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California 90089, United States.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7388-7398. doi: 10.1021/acsabm.0c00503. Epub 2020 Oct 19.
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.
局部给药作为一种规避传统化疗副作用（如高毒性和长期治疗）的方法，具有巨大的潜力。纳米级载体（即直径<100 nm）通常可以在肿瘤细胞中积累，但设计出同时具有耐久性（以在递送过程中存活）和可降解性（一旦进入细胞内就释放所载药物）的此类载体仍然是一项挑战。在本研究中，利用光响应性阴阳离子囊泡将Bcl-2 siRNA和紫杉醇共递送至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传统阴离子表面活性剂简单混合时自发形成，在紫外线照射下分解为游离表面活性剂。这使得在细胞摄取后能够光触发共载治疗药物的释放，结果表明这增强了细胞死亡和蛋白质抑制。利用动态光散射、zeta电位、小角中子散射和荧光光谱测量来确定用于包封和摄取的最佳囊泡大小、电荷、双层厚度和浓度。使用细胞活力、流式细胞术和共聚焦显微镜来证明安全有效的剂量，而通过蛋白质免疫印迹法确认了Bcl-2蛋白表达的敲低。
