摘要
树枝状大分子具有精确的三维球形纳米结构,是一种理想的药物和生物探针载体材料[1]。传统的树枝状大分子尽管具有超支化的三维结构,但是内部缺乏反应性官能团,导致其内部的空间难以被充分应用[2]。据此,本文设计合成了环糊精为核、支链上具有大量羟基官能团的新型树枝状大分子,并在其表面修饰氨基酸及肿瘤靶向基团,内部引入小分子造影剂和/或抗癌药物,制备得到肿瘤靶向的树枝状大分子磁共振成像造影剂及药物(图1)。例如,第三代树枝状大分子具有84个双键及126个羟基残基,经GPC测定其相对分子量Mn为21 KDa,通过支链修饰DTPA-Gd得到的树枝状大分子造影剂的弛豫率为10.5 mM~(-1)S~(-1),为商用造影剂马根维显的2.5倍,另外,还将其与抗癌药顺铂等结合,获得了诊疗一体化的纳米载药系统。体内、外实验表明该树枝状大分子造影剂及药物能够高效地靶向肿瘤、增强肿瘤成像,并具有较好的抗效果。
Dendrimers with will-defined 3-D spherical nanostructures are ideal nanoplatforms for drug and bioprobe delivery. All their functional groups are on the surfaces, which limits their multifunctionalization and utilization of the inner space. Herein, we developed a facile synthesis of a new dendrimer with-OH residues on the sides of its branches, and then we modified its surface with amino acid and targeting groups and the-OH residues with small molecular MRI contrast agents and anticancer drugs. The dendritic MRI contrast agents and drugs showed promising tumor contrasting and therapeutic effect.
引文
[1]Kesharwani,P.;Lyer,AK.Drug Discovery Today 2015,20(5),536-547.
[2]Svenson,S.Chem.Soc.Rev.2015,44(12),4131