Department of Obstetrics, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P. R. China.
Biomater Sci. 2017 Dec 19;6(1):200-206. doi: 10.1039/c7bm00747g.
Poly(ethylene glycol) (PEG), which is considered as a gold standard for surface modification of nanoparticles in biomedical applications, has been reported to encounter the accelerated blood clearance (ABC) phenomenon after repeated administration. Herein, as an ideal substitute for PEG, a zwitterionic peptide sequence of alternating negatively charged glutamic acid (E) and positively charged lysine (K) was designed as a good candidate for surface modification of nanoparticles without the ABC phenomenon in vivo. PEG-protected gold nanoparticles (AuNP-PEG) suffered from a serious ABC phenomenon with very fast blood clearance after repeated injection. Meanwhile, the plasma IgM and IgG levels were significantly increased after the repeated injection of AuNP-PEG. However, zwitterionic stealth peptide-protected gold nanoparticles (AuNP-EK10) could avoid the activation of the ABC phenomenon. The increase of IgM and IgG levels was not observed after the repeated injection of AuNP-EK10. More interestingly, compared to AuNP-PEG, more AuNP-EK10 could be accumulated in tumor tissues after repeated injection of the nanoparticles to tumor-bearing nude mice, which might be especially important for the design of drug nanocarriers in cancer therapy.
聚乙二醇（PEG）被认为是生物医学应用中纳米颗粒表面修饰的金标准，但在重复给药后，已报道其会出现加速血液清除（ABC）现象。在此，作为 PEG 的理想替代品，一种交替带有负电荷谷氨酸（E）和正电荷赖氨酸（K）的两性离子肽序列被设计为用于纳米颗粒表面修饰的候选物，在体内不会出现 ABC 现象。经 PEG 保护的金纳米颗粒（AuNP-PEG）在重复注射后会遭受严重的 ABC 现象，导致血液清除非常快。同时，在重复注射 AuNP-PEG 后，血浆 IgM 和 IgG 水平显著升高。然而，两性离子隐形肽保护的金纳米颗粒（AuNP-EK10）可以避免 ABC 现象的激活。在重复注射 AuNP-EK10 后，IgM 和 IgG 水平的增加并未观察到。更有趣的是，与 AuNP-PEG 相比，在向荷瘤裸鼠重复注射纳米颗粒后，更多的 AuNP-EK10 可以在肿瘤组织中积累，这对于癌症治疗中的药物纳米载体设计可能尤为重要。
