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.