纳米凝胶-蛋白质缀合物的合成
Synthesis of Nanogel-Protein Conjugates.
作者信息
Matsumoto Nicholas M, González-Toro Daniella C, Chacko Reuben T, Maynard Heather D, Thayumanavan S
机构信息
Department of Chemistry and Biochemistry and California Nanosystems Institute, 607 Charles E. Young Drive East, University of California, Los Angeles, CA 90095-1569.
Department of Chemistry, University of Massachusetts at Amherst, Amherst Massachusetts 01003.
出版信息
Polym Chem. 2013 Apr 21;4(8):2464-2469. doi: 10.1039/C3PY00085K.
The covalent conjugation of bovine serum albumin (BSA) to disulfide cross-linked polymeric nanogels is reported. Polymeric nanogel precursors were synthesized via a reversible addition-fragmentation chain transfer (RAFT) random copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and pyridyl disulfide methacrylate (PDSMA). Reaction of the p(PEGMA--PDSMA) with dithiothreitol resulted in the formation of nanogels. PDSMA serves as both a crosslinking agent and a reactive handle for the surface modification of the nanogels. Lipophilic dye, DiI, was sequestered within the nanogels by performing the crosslinking reaction in the presence of the hydrophobic molecule. Thiol-enriched BSA was conjugated to nanogels loaded with DiI via a disulfide reaction between the BSA and the surface exposed nanogel pyridyl disulfides. Conjugation was confirmed by fast protein liquid chromatography, dynamic light scattering, and agarose and polyacrylamide gel electrophoresis. We expect that this methodology is generally applicable to the preparation of nanogel-protein therapeutics.
本文报道了牛血清白蛋白（BSA）与二硫键交联的聚合物纳米凝胶的共价偶联。通过聚（乙二醇）甲基醚甲基丙烯酸酯（PEGMA）和吡啶基二硫代甲基丙烯酸酯（PDSMA）的可逆加成-断裂链转移（RAFT）自由基共聚反应合成了聚合物纳米凝胶前体。聚（PEGMA-PDSMA）与二硫苏糖醇反应生成纳米凝胶。PDSMA既作为交联剂，又作为纳米凝胶表面修饰的反应位点。通过在疏水分子存在下进行交联反应，将亲脂性染料DiI包封在纳米凝胶中。富含巯基的BSA通过BSA与纳米凝胶表面暴露的吡啶基二硫键之间的二硫键反应与负载DiI的纳米凝胶偶联。通过快速蛋白质液相色谱、动态光散射以及琼脂糖和聚丙烯酰胺凝胶电泳对偶联进行了确认。我们期望这种方法通常适用于纳米凝胶-蛋白质治疗剂的制备。
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