Department of Oncology, Clinical College of Weifang Medical University, Weifang 261031, People's Republic of China.
Int J Nanomedicine. 2020 Jul 23;15:5203-5215. doi: 10.2147/IJN.S253094. eCollection 2020.
Metformin is an ideal candidate to treat the liver tumor with insulin resistance because of its good performance in the treatment of type 2 diabetes and the advantage in cancer therapy. We aim to develop a delivery system with higher efficiency than free drug.
Metformin-bovine serum albumin (met-BSA) nanoparticles (NPs) were prepared using the anti-solvent precipitation method with a stabilizer of BSA for particle growth. The therapeutic effect of the drug was tested by the insulin-resistant HepG2 cells and C57BL/6J mice at a glucose starvation condition. The interaction mechanism of the drug and the protein during the formation of the NPs was tested using a series of spectroscopy.
Metformin and BSA formed nonporous and spherical particles of about 200 nm with proper lognormal distribution and thermostability. The cellular uptake, as well as the anti-liver cancer activities of met-BSA, was enhanced dramatically compared with the free drug. The thermodynamic studies suggested that the weak binding of metformin to BSA was governed by hydrogen bonds and van der Waals forces. Moreover, the results of synchronous, circular dichroism (CD) and three-dimensional fluorescence demonstrated that the BSA skeleton and chromophore microenvironments were changed in the presence of metformin.
Therefore, met-BSA has been proved as a simple yet effective therapeutic agent for cancer with insulin resistance, promising for future clinic translations in cancer treatment.
二甲双胍是治疗伴有胰岛素抵抗的肝肿瘤的理想候选药物，因为它在治疗 2 型糖尿病方面表现良好，并且在癌症治疗方面具有优势。我们旨在开发一种比游离药物效率更高的递送系统。
采用抗溶剂沉淀法，以 BSA 作为稳定剂促进颗粒生长，制备二甲双胍-牛血清白蛋白（met-BSA）纳米颗粒（NPs）。在葡萄糖饥饿条件下，用胰岛素抵抗 HepG2 细胞和 C57BL/6J 小鼠测试药物的治疗效果。采用一系列光谱法测试药物与蛋白质在形成 NPs 过程中的相互作用机制。
二甲双胍和 BSA 形成了约 200nm 的无孔球形颗粒，具有适当的对数正态分布和热稳定性。与游离药物相比，met-BSA 的细胞摄取率以及抗肝癌活性显著提高。热力学研究表明，二甲双胍与 BSA 的弱结合由氢键和范德华力控制。此外，同步圆二色性（CD）和三维荧光的结果表明，在存在二甲双胍的情况下，BSA 骨架和发色团微环境发生了变化。
因此，met-BSA 已被证明是一种简单而有效的治疗伴有胰岛素抵抗的癌症的药物，有望在癌症治疗的未来临床转化中得到应用。
