School of Basic Sciences, Indian Institute of Technology, Mandi, HP 175001, India.
Advanced Materials Research Centre, Indian Institute of Technology, Mandi, HP 175001, India.
ACS Appl Bio Mater. 2021 Jul 19;4(7):5776-5785. doi: 10.1021/acsabm.1c00526. Epub 2021 Jul 5.
It is practically impossible to avoid the nonspecific binding of protein to a nanocarrier when it enters a biological fluid. This hinders the chemotherapeutic efficacy of the nanocarrier to a large extent. Surface functionalization, in the recent past, helped in reducing such nonspecific interactions. However, there is a lack of understanding as to how they help in the case of nanocarriers with size <6 nm. Here, we show that the glutathione and folic acid functionalization to a small carbogenic nanocarrier leads to substantial improvement in cell internalization and chemotherapeutic efficacy. The functionalization on smaller size of the nanocarrier helped in manipulating the binding affinity of the protein, which in turn helped in easy dynamic exchange with the surrounding environment. Using fluorescence lifetime imaging, we directly visualized and mapped the released drug at a very high resolution and provide a comprehensive mechanism of the drug distribution inside a cancer cell, as a consequence of the different affinity of protein corona on the carbon nanoparticle.
当纳米载体进入生物流体时，实际上不可能避免蛋白质的非特异性结合。这在很大程度上阻碍了纳米载体的化疗效果。在最近的一段时间里，表面功能化有助于减少这种非特异性相互作用。然而，对于尺寸<6nm 的纳米载体，人们对其如何发挥作用的了解还很缺乏。在这里，我们表明，小分子碳基纳米载体的谷胱甘肽和叶酸功能化导致细胞内化和化疗效果有了实质性的提高。纳米载体的较小尺寸上的功能化有助于控制蛋白质的结合亲和力，这反过来又有助于与周围环境进行轻松的动态交换。通过荧光寿命成像，我们直接可视化并以非常高的分辨率绘制了释放的药物，并提供了由于碳纳米颗粒上的蛋白质冠的不同亲和力，药物在癌细胞内分布的全面机制。
