Anticancer Efficacy of Targeted Shikonin Liposomes Modified with RGD in Breast Cancer Cells

• Main Authors: Xianchun Wen, Jiping Li, Defu Cai, Liling Yue, Qi Wang, Li Zhou, Li Fan, Jianwen Sun, Yonghui Wu
• Format: Article
• Language: English
• Published: MDPI AG 2018-01-01
• Series: Molecules
• Subjects: shikonin; integrin αvβ3; liposomes; apoptosis; migration; targeted therapy
• Online Access: http://www.mdpi.com/1420-3049/23/2/268

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 αvβ3-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.