Key Laboratory of Functional Polymer Materials of the Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, and ‡Collaborative Innovation Center of Chemical Science and Engineering, Nankai University , Tianjin 300071, China.
ACS Appl Mater Interfaces. 2017 May 24;9(20):16767-16777. doi: 10.1021/acsami.7b00687. Epub 2017 May 10.
A reversible programmed targeting strategy could achieve high tumor accumulation due to its long blood circulation time and high cellular internalization. Here, targeting ligand-modified poly(ethylene glycol) (PEG-ligand), dibutylamines (Bu), and pyrrolidinamines (Py) were introduced on the surface of gold nanoparticles (Au NPs) for reversible shielding/deshielding of the targeting ligands by pH-responsive self-assembly. Hydrophobic interaction and steric repulsion are the main driving forces for the self-assembly/disassembly of Au NPs. The precise self-assembly (pH ≥ 7.2) and disassembly (pH ≤ 6.8) of Au NPs with different ligands could be achieved by fine-tuning the modifying molar ratio of Bu and Py (R), which followed the formula R = 1/(-0.0013X + 0.0323X + 1), in which X is the logarithm of the partition coefficient of the targeting ligand. The assembled/disassembled behavior of Au NPs at pH 7.2 and 6.8 was confirmed by transmission electron microscopy and dynamic light scattering. Enzyme-linked immunosorbent assays and cellular uptake studies showed that the ligands could be buried inside the assembly and exposed when disassembled. More importantly, this process was reversible, which provides the possibility of prolonging blood circulation by shielding ligands associated with the NPs that were effused from tumor tissue.
一种可还原的靶向策略可以实现高肿瘤积累，因为它具有长血液循环时间和高细胞内化作用。在这里，靶向配体修饰的聚乙二醇（PEG-配体）、二丁胺（Bu）和吡咯烷胺（Py）被引入金纳米粒子（Au NPs）的表面，通过 pH 响应的自组装来可逆屏蔽/去屏蔽靶向配体。疏水力和空间排斥力是 Au NPs 自组装/解组装的主要驱动力。通过精细调整 Bu 和 Py（R）的修饰摩尔比，可以实现具有不同配体的 Au NPs 的精确自组装（pH ≥ 7.2）和自组装（pH ≤ 6.8），该公式为 R = 1/(-0.0013X + 0.0323X + 1)，其中 X 是靶向配体的分配系数的对数。Au NPs 在 pH 7.2 和 6.8 下的组装/解组装行为通过透射电子显微镜和动态光散射得到证实。酶联免疫吸附试验和细胞摄取研究表明，当组装物解组装时，配体可以被埋藏在内部并暴露出来。更重要的是，这个过程是可逆的，这为通过屏蔽与从肿瘤组织渗出的 NPs 相关的配体来延长血液循环提供了可能性。
