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.

中文翻译：

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基于自组装两亲物的纳米颗粒通过 ICAM-1 介导的细胞粘附抑制肝细胞癌转移。

已经出现了纳米尺寸的药物递送系统以提高抗癌药物的治疗性能。在这里，开发了一种由两亲性前药 N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine 组成的两亲性纳米颗粒（UP12 NPs），其尺寸均一（~100 nm），具有小分子和纳米药物的优势。带正电荷的 UP12 NPs 比带负电荷的 UA NPs 显着增强了 HepG2 细胞对细胞药物的吸收。同时，UP12 和这些基于两亲物的治疗性纳米颗粒可以比 UA 和 UA NPs 更有效地诱导细胞凋亡。此外，分子对接表明UP12和细胞间粘附分子1（ICAM-1）可以很好地对接。在体内，UP12 NPs增强了肿瘤的积累，抑制了肿瘤肺转移并表现出良好的生物相容性。总体而言，UP12 或 UP12 NPs 可以开发为通过 ICAM-1 介导的细胞粘附治疗癌症转移的前瞻性药物。

重要性声明

在这项研究中，我们通过组装熊果酸哌嗪衍生物 N-[3b-acetoxy-urs-12-en-28-oyl]-amino-2-methylpiperazine（名称为 UP12 NPs），制备了具有治疗作用的两亲性纳米粒子。细胞毒性。UP12 NPs 表现出球形形态和均匀的尺寸。特别是，这些基于两亲物的治疗性纳米颗粒通过细胞间粘附分子 1 (ICAM-1) 介导的细胞粘附显着增强肿瘤积累并抑制肿瘤肺转移。