Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
ACS Nano. 2012 Feb 28;6(2):1463-72. doi: 10.1021/nn204319b. Epub 2012 Jan 19.
We present a generic and versatile method for functionalization of disulfide-stabilized PMA hydrogel capsules (HCs) with macromolecules, including a number of specific antibodies to cancer cells. Functionalization was achieved by reversible addition-fragmentation chain transfer (RAFT) polymerization of poly(N-vinyl pyrrolidone) (PVPON), which introduced biorelevant heterotelechelic end groups (thiol and amine) to the polymer chain. The PVPON with heterotelechelic end groups was conjugated to the outermost layer of PMA HCs through the thiol groups and reacted with biotin via the amine groups to generate PMA/PVPON(biotin) HCs. On the basis of the high specific interaction and high affinity between biotin and avidin, and its derivates, such as NeutrAvidin (NAv), we functionalized the PMA HCs with biotinylated antibodies. We demonstrate significantly enhanced cellular binding and internalization of the antibody (Ab)-functionalized capsules compared with control human immunoglobulin (IgG)-functionalized capsules, suggesting these capsules can specifically interact with cells through antibody/antigen recognition. We anticipate that the versatility of the functionalization approach reported in this study will assist in targeted therapeutic delivery applications.
我们提出了一种通用且多功能的方法，用于将二硫键稳定的 PMAPMA 水凝胶胶囊 (HCs) 与包括多种针对癌细胞的特异性抗体在内的大分子进行功能化。通过聚 (N-乙烯基吡咯烷酮) (PVPON) 的可逆加成-断裂链转移 (RAFT) 聚合实现了功能化，该方法向聚合物链中引入了生物相关的杂双亲末端基团（巯基和胺基）。具有杂双亲末端基团的 PVPON 通过巯基与最外层的 PMAPMA HCs 连接，并通过胺基与生物素反应，生成 PMAPVPON(生物素) HCs。基于生物素与亲和素及其衍生物（如 NeutrAvidin (NAv) 之间的高特异性相互作用和高亲和力，我们用生物素化的抗体对 PMAPMA HCs 进行了功能化。与对照的人免疫球蛋白 (IgG) 功能化胶囊相比，我们证明了抗体功能化胶囊的细胞结合和内化能力显著增强，这表明这些胶囊可以通过抗体/抗原识别特异性地与细胞相互作用。我们预计本研究中报道的功能化方法的多功能性将有助于靶向治疗药物的递送应用。
