Abstract
The treatment of malignant tumors is usually accompanied by poor prognosis due to metastasis of tumor cells. Hence, it is crucial to enhance anti-metastasis efficacy when anti-tumor treatments are conducted. It has been reported that the vascular cell adhesion molecule-1 (VCAM-1) is highly expressed on the surface of tumor cells and plays an essential role in the metastasis of tumor cells. Thus, reducing VCAM-1 expression offers hope for inhibiting the metastasis of tumor cells. Evidence has shown that succinobucol (Suc) can selectively and efficiently inhibit VCAM-1 expression. Inspired by these, we designed dual drug-loaded PLGA nanoparticles (Co-NPs) to co-deliver VCAM-1 inhibitor Suc and the chemotherapeutic doxorubicin (Dox) which could both effectively suppress primary melanoma and its lung metastases. Co-NPs were composed of PLGA encapsulated Suc and Dox as hydrophobic cores and DSPE-mPEG(2000) as surface modification materials. With an appropriate particle size (122.4 nm) and a negatively charged surface (-6.77 mV) we could achieve prolonged blood circulation. The in vitro experiments showed that Co-NPs had potent cytotoxicity against B16F10 cells and could significantly inhibit VCAM-1 expression and migration of B16F10 cells. Additionally, the in vivo experiments showed that Co-NPs could efficiently suppress not only primary melanoma but also its lung metastases. In conclusion, PLGA nanoparticles containing VCAM-1 inhibitor Suc and chemotherapeutic Dox as therapy against primary tumors and their lung metastases provides a promising drug delivery strategy for the treatment of metastatic malignant tumors.