MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, China.
ACS Appl Mater Interfaces. 2014;6(21):18930-7. doi: 10.1021/am504813f. Epub 2014 Oct 20.
The acidic microenvironment of tumor tissues has proven to be one of the major differences from other normal tissues. The near-infrared (NIR) light irradiation of aggregated gold nanoparticles in a tumor acidic pH-induced manner could then provide an effect approach to treat solid tumors with the advantage of minimizing the undesired damage to normal tissues. Although it is well-known the aggregation of larger nanoparticles will result in a better NIR photothermal effect, the preparation of pH-sensitive gold nanoparticles in large sizes remains a big challenge because of their worse dispersive stability. In this paper, we introduce a facile way to endow large gold nanoparticles with tunable pH-aggregation behaviors by modifying the nanoparticle surface with mixed-charge self-assembly monolayers compromising positively and negatively charged thiol ligands. Four different size nanoparticles were used to study the general principle of tailoring the pH-induced aggregation behaviors of mixed-charge gold nanoparticles (MC-GNPs) by adjusting the surface ligand composition. With proper surface ligand composition, the MC-GNPs in four different sizes that all exhibited aggregation at tumor acidic pH were obtained. The biggest MC-GNPs showed the most encouraging aggregation-enhanced photothermal efficacy in vitro when they formed aggregates. The mixed-charge self-assembled monolayers were then proved as a facile method to design pH-induced aggregation of large gold nanoparticles for better NIR photothermal cancer therapy.
肿瘤组织的酸性微环境已被证明是其与其他正常组织的主要区别之一。在肿瘤酸性 pH 诱导下，聚集的金纳米粒子的近红外（NIR）光照射可以为治疗实体瘤提供一种有效的方法，其优点是最小化对正常组织的不必要损伤。虽然众所周知较大的纳米粒子的聚集会导致更好的 NIR 光热效应，但由于其较差的分散稳定性，大尺寸的 pH 敏感金纳米粒子的制备仍然是一个巨大的挑战。在本文中，我们介绍了一种通过用带正电荷和负电荷的硫醇配体混合的混合电荷自组装单层来修饰纳米粒子表面，从而赋予大尺寸金纳米粒子可调 pH 聚集行为的简便方法。我们使用了四种不同尺寸的纳米粒子来研究通过调整表面配体组成来调整混合电荷金纳米粒子（MC-GNPs）的 pH 诱导聚集行为的一般原理。通过适当的表面配体组成，我们获得了在肿瘤酸性 pH 下聚集的四种不同尺寸的 MC-GNPs。当形成聚集体时，最大的 MC-GNPs 在体外表现出最令人鼓舞的聚集增强光热效果。然后证明混合电荷自组装单层是设计用于更好的 NIR 光热癌症治疗的大尺寸金纳米粒子 pH 诱导聚集的简便方法。
