Chen Hongwei, Zou Hao, Paholak Hayley J, Ito Masayuki, Qian Wei, Che Yong, Sun Duxin
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109 ; Department of Pharmaceutical Sciences, College of Pharmacy, Second Military Medical University, 325 Guo He Road, Shanghai 200433, PR China.
Polym Chem. 2014 Apr 21;5(8):2768-2773. doi: 10.1039/C3PY01652H.
Nanoparticles designed for biomedical applications are often coated with polymers containing reactive functional groups, such as -COOH and -NH, to conjugate targeting ligands or drugs. However, introducing highly charged surfaces promotes binding of the nanoparticles to biomolecules in biological systems through ionic interactions, causing the nanoparticles to aggregate in biological environments and consequently undergo strong non-specific binding to off-target cells and tissues. Developing a unique polymer with neutral surfaces that can be further functionalized directly would be critical to develop suitable nanomaterials for nanomedicine. Here, we report a thiol-reactive amphiphilic block copolymer poly(ethylene oxide)-block-poly(pyridyldisulfide ethylmeth acrylate) (PEO--PPDSM) for coating gold nanoparticles (AuNPs). The resultant polymer-coated AuNPs have almost neutral surfaces with slightly negative zeta potentials from -10 to 0 mV over a wide pH range from 2 to 12. Although the zeta potential is close to zero we show that the PEO--PPDSM copolymer-coated AuNPs have both good stability in various physiological conditions and reduced non-specific adsorption of proteins/biomolecules. Because of the multiple pyridyldisulfide groups on the PPDSM block, these individually dispersed nanocomplexes with an overall hydrodynamic size around 43.8 nm can be directly functionalized via disulfide-thiol exchange chemistry.
用于生物医学应用的纳米颗粒通常会被含有反应性功能基团（如 -COOH 和 -NH）的聚合物包覆，以便缀合靶向配体或药物。然而，引入高电荷表面会通过离子相互作用促进纳米颗粒与生物系统中的生物分子结合，导致纳米颗粒在生物环境中聚集，进而与非靶细胞和组织发生强烈的非特异性结合。开发一种具有中性表面且可直接进一步功能化的独特聚合物对于开发适用于纳米医学的纳米材料至关重要。在此，我们报告一种用于包覆金纳米颗粒（AuNPs）的硫醇反应性两亲嵌段共聚物聚（环氧乙烷）-嵌段-聚（吡啶二硫代乙基甲基丙烯酸酯）（PEO-b-PPDSM）。所得的聚合物包覆的 AuNPs 具有几乎中性的表面，在 2 至 12 的宽 pH 范围内，其zeta 电位略带负电，从 -10 到 0 mV。尽管 zeta 电位接近零，但我们表明 PEO-b-PPDSM 共聚物包覆的 AuNPs 在各种生理条件下均具有良好的稳定性，并且蛋白质/生物分子的非特异性吸附减少。由于 PPDSM 嵌段上存在多个吡啶二硫基团，这些整体水动力尺寸约为 43.8 nm 的单独分散的纳米复合物可通过二硫键-硫醇交换化学直接进行功能化。
