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利用谷胱甘肽敏感的阿霉素偶联糖化牛血清白蛋白纳米粒研发针对乳腺癌的靶向药物递送载体。

Developing targeted drug delivery carriers for breast cancer using glutathione-sensitive doxorubicin-coupled glycated bovine serum albumin nanoparticles.

机构信息

Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.

Department of Life Science, Fu-Jen Catholic University, Xinzhuang Dist., New Taipei City 24205, Taiwan.

出版信息

Int J Biol Macromol. 2023 Sep 30;249:126114. doi: 10.1016/j.ijbiomac.2023.126114. Epub 2023 Aug 3.

Abstract

Incorporation of the nano-based carriers into drug delivery provides a promising alternative to overcome the limitations of the conventional chemotherapy. Doxorubicin (DOXO) is an effective chemotherapeutic drug widely used in chemotherapy for breast cancer treatment. A globular protein bovine serum albumin (BSA) holds great potential as carriers in pharmaceutical applications. This work is aimed at developing the DOXO-coupled glycated BSA nanoparticles via desolvation method for improving the capability of targeting the GLUT5 transporters over-expressed on breast cancer cells. Fructosamine assay and Fourier transform infrared spectroscopy were employed to determine the content of fructosamine structure and structural changes on the surfaces of nanoparticles, respectively. Additionally, the synthesized BSA nanoparticles were further characterized by electron microscopy and dynamic light scattering. Results revealed that the DOXO-coupled glycated BSA nanoparticles were spherically shaped with a hydrodynamic diameter of ~60.74 nm and a ζ-potential of ~ - 42.20 mV. Moreover, the DOXO release behavior of as-synthesized DOXO-coupled glycated BSA nanoparticles was examined under different conditions. Finally, the DOXO-coupled glycated BSA nanoparticles were found to exhibit cytotoxicity toward both MCF-7 and MDA-MB-231 cells. Our findings evidently suggested that the drug-coupled glycated BSA nanoparticles serve as the potential candidates for targeted drug delivery platform used in breast cancer therapy.

摘要

将基于纳米的载体纳入药物输送为克服传统化疗的局限性提供了一种有前途的替代方法。阿霉素(DOXO)是一种有效的化疗药物,广泛用于乳腺癌的化疗。球形蛋白质牛血清白蛋白(BSA)作为药物应用中的载体具有很大的潜力。这项工作旨在通过去溶剂化方法开发 DOXO 偶联糖化 BSA 纳米颗粒,以提高针对在乳腺癌细胞上过表达的 GLUT5 转运体的靶向能力。果糖胺测定法和傅里叶变换红外光谱分别用于确定纳米颗粒表面上的果糖胺结构含量和结构变化。此外,通过电子显微镜和动态光散射进一步表征合成的 BSA 纳米颗粒。结果表明,DOXO 偶联糖化 BSA 纳米颗粒呈球形,水动力直径约为 60.74nm,ζ-电位约为-42.20mV。此外,还研究了在不同条件下合成的 DOXO 偶联糖化 BSA 纳米颗粒的 DOXO 释放行为。最后,发现 DOXO 偶联糖化 BSA 纳米颗粒对 MCF-7 和 MDA-MB-231 细胞均具有细胞毒性。我们的研究结果表明,载药偶联糖化 BSA 纳米颗粒可作为用于乳腺癌治疗的靶向药物输送平台的潜在候选物。

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