MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
Adv Healthc Mater. 2014 Sep;3(9):1439-47. doi: 10.1002/adhm.201300617. Epub 2014 Feb 18.
Mixed-charge zwitterionic surface modification shows great potential as a simple strategy to fabricate nanoparticle (NP) surfaces that are nonfouling. Here, the in vivo fate of 16 nm mixed-charge gold nanoparticles (AuNPs) is investigated, coated with mixed quaternary ammonium and sulfonic groups. The results show that mixed-charge AuNPs have a much longer blood half-life (≈30.6 h) than do poly(ethylene glycol) (PEG, M¯w = 2000) -coated AuNPs (≈6.65 h) and they accumulate in the liver and spleen far less than do the PEGylated AuNPs. Using transmission electron microscopy, it is further confirmed that the mixed-charge AuNPs have much lower uptake and different existing states in liver Kupffer cells and spleen macrophages one month after injection compared with the PEGylated AuNPs. Moreover, these mixed-charge AuNPs do not cause appreciable toxicity at this tested dose to mice in a period of 1 month as evidenced by histological examinations. Importantly, the mixed-charge AuNPs have higher accumulation and slower clearance in tumors than do PEGylated AuNPs for times of 24-72 h. Results from this work show promise for effectively designing tumor-targeting NPs that can minimize reticuloendothelial system clearance and circulate for long periods by using a simple mixed-charge strategy.
混合电荷两性离子表面修饰作为一种简单的策略，具有很大的潜力来制备抗污的纳米颗粒（NP）表面。在这里，研究了带有混合季铵盐和磺酸基团的 16nm 混合电荷金纳米颗粒（AuNPs）的体内命运。结果表明，与聚乙二醇（PEG，M¯w = 2000）包覆的 AuNPs（≈6.65 h）相比，混合电荷 AuNPs 的血液半衰期（≈30.6 h）长得多，它们在肝脏和脾脏中的积累也远远少于 PEG 化的 AuNPs。使用透射电子显微镜进一步证实，与 PEG 化的 AuNPs 相比，注射一个月后，混合电荷 AuNPs 在肝枯否细胞和脾巨噬细胞中的摄取量更低，存在状态也不同。此外，在 1 个月的时间内，这些混合电荷 AuNPs 在小鼠中以测试剂量不会引起明显的毒性，这一点可以通过组织学检查得到证实。重要的是，与 PEG 化的 AuNPs 相比，混合电荷 AuNPs 在 24-72 h 的时间内具有更高的肿瘤积累和更缓慢的清除速度。这项工作的结果表明，通过使用简单的混合电荷策略，可以有效地设计出能够最小化网状内皮系统清除并长时间循环的肿瘤靶向 NP。
