Departments of Chemistry, Chemical Engineering, and Materials Science & Engineering, Laboratory for Synthetic-Biologic Interactions , Texas A&M University , College Station , Texas 77842 , United States.
Department of Pharmaceutics, Faculty of Pharmacy , Assiut University , 71515 Assiut , Egypt.
Langmuir. 2019 Feb 5;35(5):1503-1512. doi: 10.1021/acs.langmuir.8b02033. Epub 2018 Oct 22.
A zwitterionic polyphosphoester (zPPE), specifically l-cysteine-functionalized poly(but-3-yn-1-yloxy)-2-oxo-1,3,2-dioxaphospholane (zPBYP), has been developed as a poly(ethylene glycol) (PEG) alternative coating material for gold nanoparticles (AuNPs), the most extensively investigated metal nanoparticulate platform toward molecular imaging, photothermal therapy, and drug delivery applications. Thiol-yne conjugation of cysteine transformed an initial azido-terminated and alkynyl-functionalized PBYP homopolymer into zPBYP, offering hydrolytic degradability, biocompatibility, and versatile reactive moieties for installation of a range of functional groups. Despite minor degradation during purification, zPPEs were able to stabilize AuNPs presumably through multivalent interactions between combinations of the side chain zwitterions (thioether and phosphoester groups of the zPPEs with the AuNPs). P NMR studies in DO revealed ca. 20% hydrolysis of the phosphoester moieties of the repeat units had occurred during the workup and purification by aqueous dialysis at pH 3 over ca. 1 d, as observed by the P signal of the phosphotriesters resonating at ca. -0.5 to -1.7 shifting downfield to ca. 1.1 to -0.4 ppm, attributed to transformation to phosphates. Further hydrolysis of side chain and backbone units proceeded to an extent of ca. 75% over the next 2 d in nanopure water (pH 5-6). The NMR degradation results were consistent with the broadening and red-shift of the surface plasmon resonance (SPR) observed by UV-vis spectroscopy of the zPPE-coated AuNPs in water over time. All AuNP formulations in this study, including those with citrate, PEG, and zPPE coatings, exhibited negligible immunotoxicity, as determined by cytokine overexpression in the presence of the nanostructures relative to those in cell culture medium. Notably, the zPPE-coated AuNPs displayed superior antifouling properties, as assessed by the extent of cytokine adsorption relative to both the PEGylated and citrate-coated AuNPs. Taken together, the physicochemical and biological evaluations of zPPE-coated AuNPs in conjunction with PEGylated and citrate-coated analogues indicate the promise of zPPEs as favorable alternatives to PEG coatings, with negligible immunotoxicity, good antifouling performance, and versatile reactive groups that enable the preparation of highly tailored nanomaterials for diverse applications.
一种两性离子聚膦酸酯（zPPE），特别是半胱氨酸功能化的聚（丁-3-炔-1-氧基）-2-氧代-1,3,2-二氧杂磷杂环戊烷（zPBYP），已被开发为金纳米粒子（AuNPs）的聚乙二醇（PEG）替代涂层材料，AuNPs 是最广泛研究的用于分子成像、光热治疗和药物输送应用的金属纳米颗粒平台。半胱氨酸的硫醇-炔键合将初始末端叠氮化物和炔基功能化的 PBYP 均聚物转化为 zPBYP，提供了水解降解性、生物相容性和用于安装一系列官能团的多功能反应性基团。尽管在纯化过程中发生了轻微的降解，但 zPPE 能够稳定 AuNPs，这可能是通过侧链两性离子（zPPE 的硫醚和磷酸酯基团与 AuNPs 之间的组合）之间的多价相互作用实现的。在 DO 中的 P NMR 研究表明，在 pH 3 下通过水性透析进行的工作和纯化过程中，约 20%的重复单元的磷酸酯部分发生水解，这可以通过磷酰三酯的 P 信号共振在约-0.5 至-1.7 移至约 1.1 至-0.4 ppm 来观察到，这归因于向磷酸盐的转化。在接下来的 2 天中，侧链和主链单元的进一步水解进行到约 75%的程度在纳米纯水中（pH 5-6）。NMR 降解结果与通过时间分辨紫外-可见光谱法观察到的 zPPE 涂层 AuNPs 在水中的表面等离子体共振（SPR）的展宽和红移一致。本研究中的所有 AuNP 制剂，包括具有柠檬酸、PEG 和 zPPE 涂层的制剂，与纳米结构在细胞培养基中的细胞因子过表达相比，表现出可忽略不计的免疫毒性。值得注意的是，与聚乙二醇化和柠檬酸涂层的 AuNPs 相比，zPPE 涂层的 AuNPs 表现出优异的抗污染特性。综上所述，zPPE 涂层 AuNPs 的物理化学和生物学评价与聚乙二醇化和柠檬酸涂层类似物相结合，表明 zPPE 作为 PEG 涂层的有利替代品具有很大的应用前景，具有可忽略不计的免疫毒性、良好的抗污染性能和多功能反应性基团，可用于制备用于各种应用的高度定制的纳米材料。
