Department of Bioengineering, Clemson University, South Carolina 29634, USA.
Biotechnol Bioeng. 2011 Feb;108(2):243-52. doi: 10.1002/bit.22958.
Poly(butyl cyanoacrylate) (PBCA) nanoparticles (NPs) can penetrate blood-brain barrier providing the means for drug delivery to the central nervous system. Here, we study attachment of superoxide dismutase (SOD) and anti-glutamate N-methyl D-aspartate receptor 1 (NR1) antibody to PBCA NPs with the ultimate goal to design neuroprotective therapeutics for treatment of secondary spinal cord injury. Synthesis of monodispersed, ∼200 nm-diameter PBCA NPs was performed using polymerization at pH 2.0 with Dextran 70,000 as the stabilizer. Sulfo-HSAB spacers were used to covalently attach SOD and NR1 antibodies to the dextran-coated NPs. The prepared protein-NP conjugates possessed SOD activity and were capable of binding to rat cerebellar neurons. Thus, SOD and NR1 antibodies may be simultaneously attached to PBCA NPs while retaining at least a fraction of enzymatic activity and receptor-binding ability. The conjugates showed neuroprotective efficacy in vitro with rat cerebellar cell cultures challenged by superoxide.
聚氰基丙烯酸正丁酯（PBCA）纳米颗粒（NPs）可以穿透血脑屏障，为向中枢神经系统输送药物提供了途径。在这里，我们研究了超氧化物歧化酶（SOD）和抗谷氨酸 N-甲基-D-天冬氨酸受体 1（NR1）抗体与 PBCA NPs 的附着，最终目的是设计用于治疗继发性脊髓损伤的神经保护治疗方法。使用在 pH 2.0 下聚合的方法，并使用 Dextran 70000 作为稳定剂，制备了单分散的、直径约 200nm 的 PBCA NPs。使用 Sulfo-HSAB 间隔臂将 SOD 和 NR1 抗体共价连接到葡聚糖涂层的 NPs 上。所制备的蛋白-NP 缀合物具有 SOD 活性，并且能够与大鼠小脑神经元结合。因此，SOD 和 NR1 抗体可以同时附着到 PBCA NPs 上，同时保留至少一部分酶活性和受体结合能力。在超氧化物挑战的大鼠小脑细胞培养物中，该缀合物显示出体外神经保护功效。
