Self-assembled amphiphile-based nanoparticles for the inhibition of hepatocellular carcinoma metastasis via ICAM-1 mediated cell adhesion.

Nanosized drug delivery systems have emerged to improve the therapeutic performance of anticancer drugs. Here, an amphiphile-based nanoparticle consisting of amphiphilic prodrug N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine was developed (UP12 NPs) with uniform sizes (~100 nm), which possessed the advantages of small molecules and nanomedicine. The positively charged UP12 NPs significantly enhanced the cellular drug uptake on HepG2 cells than negatively charged UA NPs. Meanwhile, UP12 and these therapeutic amphiphile-based nanoparticles could induce cell apoptosis more efficiently than that of UA and UA NPs. Moreover, molecular docking demonstrated that the UP12 and intercellular adhesion molecule 1 (ICAM-1) could dock well. UP12 and UP12 NPs significantly decreased the mRNA expression of ICAM-1 and inhibited the migration and adhesion of liver cancer cells (HepG2 cells), which indicated that UP12 might be one of the potential ICAM-1 inhibitors. In vivo, UP12 NPs enhanced tumor accumulation, inhibited tumor lung metastasis and showed good biocompatibility. Overall, UP12 or UP12 NPs could be developed as prospective drugs for cancer metastasis therapy via ICAM-1 mediated cell adhesion. STATEMENT OF SIGNIFICANCE: In this study, we fabricated the therapeutic amphiphile-based nanoparticles by assembly of ursolic acid piperazine derivative N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine (name as UP12 NPs) with low cytotoxicity. UP12 NPs exhibited spherical morphology and uniform sizes. Particularly, these therapeutic amphiphile-based nanoparticles significantly enhanced tumor accumulation and inhibited tumor lung metastases via intercellular adhesion molecule 1 (ICAM-1) mediated cell adhesion.

A study to evaluate herb-drug interaction underlying mechanisms: An investigation of ginsenosides attenuating the effect of warfarin on cardiovascular diseases.

Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.