Waghmare Manik N, Qureshi Tazeen S, Krishna C Murali, Pansare Kshama, Gadewal Nikhil, Hole Arti, Dongre Prabhakar M
Department of Biophysics, University of Mumbai, Mumbai, Maharashtra, India.
Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Navi Mumbai, Maharashtra, India.
J Biomol Struct Dyn. 2022 Aug;40(13):6193-6210. doi: 10.1080/07391102.2021.1879270. Epub 2021 Jan 29.
The protein-nanoparticle interface plays a crucial role in drug binding and stability, in turn enhancing efficacy in targeted drug delivery. In the present study, whey protein β-lactoglobulin (BLG) is conjugated with gold nanoparticles (AuNP) and its interaction with curcumin (CUR) and gemcitabine (GEM) has been explored. Further, AuNP-BLG conjugate interactions with anticancer drugs were characterized using dynamic light scattering (DLS), zeta potential, UV-visible, Raman spectroscopy, fluorescence, circular dichroism along with molecular dynamics simulation. The cytotoxicity studies were performed using breast cancer cell lines (MCF-7). ∼8 µM of BLG resides on AuNP (∼29 nm) surface revealed by DLS. Raman scattering of AuNP-BLG conjugate showed orientation of the central calyx of BLG towards solvent. BLG fluorescence confirmed the interaction between AuNP-BLG conjugate with drugs and indicated strong binding and affinity (for CUR and for GEM , enhanced in the presence of AuNP. CD and Raman analysis exhibited selective hydrophilic and hydrophobic conformations induced by drug binding. Computational studies on BLG-drug complexes revealed that the residues Pro38, Leu39 and Met107 are largely associated with CUR binding, while GEM interaction is via hydrophilic contacts which significantly matches with spectroscopic investigation. IC values were calculated for all components of this loading system on MCF-7. The possible mechanisms of interaction between AuNP-BLG with anticancer drugs has been explored at the molecular level. We believe that these conjugates could be considered in the targeted drug delivery studies for cancer research.Communicated by Ramaswamy H. Sarma.
蛋白质-纳米颗粒界面在药物结合和稳定性方面起着关键作用，进而提高靶向药物递送的效果。在本研究中，乳清蛋白β-乳球蛋白（BLG）与金纳米颗粒（AuNP）共轭，并探索了其与姜黄素（CUR）和吉西他滨（GEM）的相互作用。此外，利用动态光散射（DLS）、zeta电位、紫外可见光谱、拉曼光谱、荧光、圆二色性以及分子动力学模拟对AuNP-BLG共轭物与抗癌药物的相互作用进行了表征。使用乳腺癌细胞系（MCF-7）进行了细胞毒性研究。DLS显示约8 μM的BLG存在于AuNP（约29 nm）表面。AuNP-BLG共轭物的拉曼散射表明BLG中央花萼朝向溶剂的取向。BLG荧光证实了AuNP-BLG共轭物与药物之间的相互作用，并表明存在强结合和亲和力（对于CUR 和对于GEM ，在AuNP存在下增强）。圆二色性和拉曼分析显示药物结合诱导了选择性的亲水和疏水构象。对BLG-药物复合物的计算研究表明，残基Pro38、Leu39和Met107在很大程度上与CUR结合相关，而GEM的相互作用是通过亲水接触，这与光谱研究结果显著匹配。计算了该负载系统所有组分对MCF-7的IC值。在分子水平上探索了AuNP-BLG与抗癌药物之间相互作用的可能机制。我们认为这些共轭物可用于癌症研究的靶向药物递送研究。由Ramaswamy H. Sarma传达。
