Public Health College, Harbin Medical University, Harbin 150081, China.
Research Institute of Medicine & Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.
Molecules. 2018 Jan 29;23(2):268. doi: 10.3390/molecules23020268.
Shikonin (SHK) has been proven to have a good anti-tumor effect. However, poor water solubility and low bioavailability limit its wide application in clinical practice. In this study, to overcome these drawbacks, RGD-modified shikonin-loaded liposomes (RGD-SSLs-SHK) were successfully prepared. It exhibited excellent physicochemical characteristics including particle size, zeta potential, encapsulation efficiency, and delayed release time. Meanwhile, the targeting activity of the RGD-modified liposomes was demonstrated by flow cytometry and confocal microscopy in the αβ₃-positive MDA-MB-231 cells. Besides exhibiting greater cytotoxicity in vitro, compared with non-targeted shikonin-loaded liposomes (SSLs-SHK), RGD-SSLs-SHK could also evidently induce apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. It could also inhibit cell proliferation, migration, invasion, and adhesion by reducing the expression of MMP-9 and the level of NF-κB p65, but did not affect the expression of MMP-2 in the MDA-MB-231 cells. Therefore, these findings indicated that the strategy to use RGD-modified liposomes as carriers for targeted delivery of shikonin is a very promising approach to achieve breast cancer targeted therapy.
紫草素（SHK）已被证明具有良好的抗肿瘤作用。然而，较差的水溶性和低生物利用度限制了其在临床实践中的广泛应用。在这项研究中，为了克服这些缺点，成功制备了 RGD 修饰的紫草素载脂蛋白（RGD-SSLs-SHK）。它表现出出色的物理化学特性，包括粒径、Zeta 电位、包封效率和延迟释放时间。同时，通过流式细胞术和共聚焦显微镜在 αβ₃阳性 MDA-MB-231 细胞中证明了 RGD 修饰的脂质体的靶向活性。与非靶向紫草素载脂蛋白（SSLs-SHK）相比，RGD-SSLs-SHK 在体外表现出更强的细胞毒性，还可以通过降低 Bcl-2 的表达和增加 Bax 的表达来明显诱导细胞凋亡。它还可以通过降低 MMP-9 的表达和 NF-κB p65 的水平来抑制细胞增殖、迁移、侵袭和黏附，但不影响 MDA-MB-231 细胞中 MMP-2 的表达。因此，这些发现表明，使用 RGD 修饰的脂质体作为载体进行紫草素靶向递药的策略是实现乳腺癌靶向治疗的一种很有前途的方法。
