Vinluan Rodrigo D, Yu Mengxiao, Gannaway Melissa, Sullins Justin, Xu Jing, Zheng Jie
Department of Chemistry, The University of Texas at Dallas , Richardson, Texas 75080, United States.
Bioconjug Chem. 2015 Dec 16;26(12):2435-41. doi: 10.1021/acs.bioconjchem.5b00490. Epub 2015 Oct 14.
In the native physiological environment, inorganic nanoparticles (NPs) often induce nonspecific protein adsorption, which could significantly alter the function of the proteins they labeled. As a result, small fluorescent dyes are still widely used in the imaging of proteins in animals due to their minimal interference with protein function. Here, we used monomeric insulin as a model and compared its bioactivity before and after labeling with renal-clearable near-infrared-emitting gold NPs. These NPs were chosen because they have high resistance to serum protein adsorption and low nonspecific accumulation. We have found that a 1:1 insulin-NP ratio can be achieved, where the insulin-NPs show minimal serum protein binding with fully retained bioactivity comparable to that of unlabeled insulin. These results show a proof of concept that renal-clearable NPs can behave like small molecules in protein labeling without changing the individual protein's function, laying down a foundation for in vivo tracking of proteins with multimodality imaging techniques.
在天然生理环境中，无机纳米颗粒（NPs）常常会诱导非特异性蛋白质吸附，这可能会显著改变它们所标记蛋白质的功能。因此，小型荧光染料由于对蛋白质功能的干扰最小，仍被广泛用于动物体内蛋白质成像。在此，我们以单体胰岛素为模型，比较了用可经肾脏清除的近红外发光金纳米颗粒标记前后胰岛素的生物活性。选择这些纳米颗粒是因为它们对血清蛋白吸附具有高抗性且非特异性积累低。我们发现可以实现胰岛素与纳米颗粒1:1的比例，此时胰岛素-纳米颗粒与血清蛋白的结合最少，且具有与未标记胰岛素相当的完全保留的生物活性。这些结果证明了一个概念，即可经肾脏清除的纳米颗粒在蛋白质标记中可以表现得像小分子一样，而不会改变单个蛋白质的功能，为利用多模态成像技术在体内追踪蛋白质奠定了基础。
