Key Laboratory of Functional Polymer Materials of Ministry of Education and Institute of Polymer Chemistry, Nankai University Collaborative Innovation Center of Chemical Science and Engineering , Tianjin 300071, China.
ACS Appl Mater Interfaces. 2014 Oct 22;6(20):17865-76. doi: 10.1021/am5045339. Epub 2014 Sep 30.
A new approach to shield/deshield ligands for controllable tumor targeting was reported, which was based on amphiphilic self-assembly and disassembly of gold nanoparticles (Au NPs). Thanks to the excellent pH response of the system, glycyrrhetinic acid (GA) ligands can be buried inside the Au NPs' assembly at normal tissue pH (pH 7.4), while exposed when the nanostructure is disassembled at tumor extracellular pH (pHe 6.8). Hydrophobic GA molecules not only acted as ligands targeting tumor cells but also provided the major interparticle attractive force for Au NPs' assembling. An ordered assembly of Au NPs with regular shape, proper size and ultrasharp pH sensitivity (ΔpH ∼ 0.2) was achieved by fine-tuning of materials modified on Au NPs. Mechanism studies for assembly and disassembly of Au NPs indicated the possibility of a GA shield when the assembly formed, which was further demonstrated by bovine serum albumin absorption and cellular uptake. The assembly/disassembly process was reversible within extrinsic pH changes, which provides a perspective for reversible tumor targeting.
一种新的用于可控肿瘤靶向的屏蔽/去屏蔽配体的方法被报道，该方法基于两亲性的金纳米粒子（Au NPs）的自组装和去组装。由于该体系具有优异的 pH 响应性，在正常组织 pH（pH 7.4）下，甘草次酸（GA）配体可以埋藏在 Au NPs 的组装体中，而在肿瘤细胞外 pH（pHe 6.8）下，纳米结构分解时，GA 配体可以暴露出来。疏水 GA 分子不仅作为靶向肿瘤细胞的配体，而且为 Au NPs 的组装提供了主要的颗粒间吸引力。通过精细调整 Au NPs 上修饰的材料，实现了具有规则形状、适当尺寸和超灵敏 pH 值（ΔpH∼0.2）的 Au NPs 的有序组装。Au NPs 的组装和解组装的机制研究表明，当组装形成时，GA 可能会形成屏蔽，这一点通过牛血清白蛋白吸收和细胞摄取进一步得到证实。在外部 pH 值变化的情况下，组装/解组装过程是可逆的，这为可逆的肿瘤靶向提供了一种可能。
