Budhathoki-Uprety Januka, Harvey Jackson D, Isaac Elizabeth, Williams Ryan M, Galassi Thomas V, Langenbacher Rachel E, Heller Daniel A
Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
J Mater Chem B. 2017 Aug 28;5(32):6637-6644. doi: 10.1039/c7tb00695k. Epub 2017 Jun 21.
Carbon nanotube-based molecular probes, imaging agents, and biosensors in cells and in vivo continue to garner interest as investigational tools and clinical devices due to their unique photophysical properties. Surface chemistry modulation of nanotubes plays a critical role in determining stability and interaction with biological systems both in vitro and in vivo. Among the many parameters that influence the biological fate of nanomaterials, surface charge is particularly influential due to direct electrostatic interactions with components of the cell membrane as well as proteins in the serum, which coat the nanoparticle surface in a protein corona and alter nanoparticle-cell interactions. Here, we modulated functional moieties on a helical polycarbodiimide polymer backbone that non-covalently suspended the nanotubes in aqueous media. By derivatizing the polymer with either primary amine or carboxylic acid side chains, we obtained nanotube complexes that present net surface charges of opposite polarity at physiological pH. Using these materials, we found that the uptake of carbon nanotubes in these cells is highly dependent on charge, with cationic nanotubes efficiently internalized into cells compared to the anionic nanotubes. Furthermore, we found that serum proteins drastically influenced cell uptake of the anionic nanotubes, while the effect was not prominent for the cationic nanotubes. Our findings have implications for improved engineering of drug delivery devices, molecular probes, and biosensors.
基于碳纳米管的分子探针、成像剂以及细胞和体内生物传感器,由于其独特的光物理性质,作为研究工具和临床设备持续受到关注。纳米管的表面化学调控在决定其在体外和体内与生物系统的稳定性及相互作用方面起着关键作用。在众多影响纳米材料生物学命运的参数中,表面电荷因其与细胞膜成分以及血清中蛋白质的直接静电相互作用而具有特别重要的影响,血清中的蛋白质会在纳米颗粒表面形成蛋白质冠层并改变纳米颗粒与细胞的相互作用。在此,我们对螺旋状聚碳二亚胺聚合物主链上的功能基团进行调控,该聚合物主链能将纳米管非共价悬浮于水性介质中。通过用伯胺或羧酸侧链对聚合物进行衍生化,我们得到了在生理pH值下呈现相反极性净表面电荷的纳米管复合物。使用这些材料,我们发现这些细胞对碳纳米管的摄取高度依赖于电荷,与阴离子型纳米管相比,阳离子型纳米管能高效内化进入细胞。此外,我们发现血清蛋白对阴离子型纳米管的细胞摄取有显著影响,而对阳离子型纳米管的影响并不明显。我们的研究结果对改进药物递送装置、分子探针和生物传感器的工程设计具有启示意义。