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DOX 或 PTX 与乳白蛋白作为递送载体相互作用机制的生物物理研究。

A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier.

机构信息

Institute of Biochemistry and Biophysics, University of Tehran, Mailbox, 13145-1384, Tehran, Iran.

Department of Life Science Engineering, Faculty of New Sciences & Technologies, University of Tehran, Tehran, Iran.

出版信息

Sci Rep. 2018 Nov 26;8(1):17345. doi: 10.1038/s41598-018-35559-1.

DOI:10.1038/s41598-018-35559-1
PMID:30478403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6255783/
Abstract

Doxorubicin and paclitaxel, two hydrophobic chemotherapeutic agents, are used in cancer therapies. Presence of hydrophobic patches and a flexible fold could probably make α-Lactalbumin a suitable carrier for hydrophobic drugs. In the present study, a variety of thermodynamic, spectroscopic, computational, and cellular techniques were applied to assess α-lactalbumin potential as a carrier for doxorubicin and paclitaxel. According to isothermal titration calorimetry data, the interaction between α-lactalbumin and doxorubicin or paclitaxel is spontaneous and the K (M) value for the interaction of α-lactalbumin and paclitaxel is higher than that for doxorubicin. Differential scanning calorimetry and anisotropy results indicated formation of α-lactalbumin complexes with doxorubicin or paclitaxel. Furthermore, molecular docking and dynamic studies revealed that TRPs are not involved in α-Lac's interaction with Doxorubicin while TRP 60 interacts with paclitaxel. Based on Pace analysis to determine protein thermal stability, doxorubicin and paclitaxel induced higher and lower thermal stability in α-lactalbumin, respectively. Besides, fluorescence lifetime measurements reflected that the interaction between α-lactalbumin with doxorubicin or paclitaxel was of static nature. Therefore, the authors hypothesized that α-lactalbumin could serve as a carrier for doxorubicin and paclitaxel by reducing cytotoxicity and apoptosis which was demonstrated during our in vitro cell studies.

摘要

阿霉素和紫杉醇是两种疏水性化疗药物，用于癌症治疗。疏水性补丁和灵活的折叠可能使α-乳白蛋白成为疏水性药物的合适载体。在本研究中，应用了各种热力学、光谱学、计算和细胞技术来评估α-乳白蛋白作为阿霉素和紫杉醇载体的潜力。根据等温滴定量热法数据，α-乳白蛋白与阿霉素或紫杉醇的相互作用是自发的，α-乳白蛋白与紫杉醇的相互作用的 K (M) 值高于阿霉素。差示扫描量热法和各向异性结果表明形成了α-乳白蛋白与阿霉素或紫杉醇的复合物。此外，分子对接和动态研究表明，TRP 不参与α-Lac 与阿霉素的相互作用，而 TRP60 与紫杉醇相互作用。基于确定蛋白质热稳定性的 Pace 分析，阿霉素和紫杉醇分别诱导α-乳白蛋白更高和更低的热稳定性。此外，荧光寿命测量反映了α-乳白蛋白与阿霉素或紫杉醇之间的相互作用是静态的。因此，作者假设α-乳白蛋白可以通过降低细胞毒性和细胞凋亡来作为阿霉素和紫杉醇的载体，这在我们的体外细胞研究中得到了证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/005e/6255783/e9d2af13985f/41598_2018_35559_Fig15_HTML.jpg
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