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.

中文翻译：

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两性离子隐形肽保护的金纳米粒子可实现长循环，而不会出现加速的血液清除现象†

聚乙二醇（PEG）被认为是生物医学应用中纳米颗粒表面改性的金标准，据报道在重复给药后会遇到加速的血液清除（ABC）现象。在本文中，作为理想的PEG替代品，交替选择带负电荷的谷氨酸（E）和带正电荷的赖氨酸（K）的两性离子肽序列可作为体内无ABC现象的纳米粒子表面修饰的良好候选者。PEG保护的金纳米颗粒（AuNP-PEG）遭受严重的ABC现象，重复注射后血液清除速度非常快。同时，重复注射AuNP-PEG后血浆IgM和IgG水平明显升高。但是，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。重复注射AuNP-EK10后，未观察到IgM和IgG水平的增加。更有趣的是，与AuNP-PEG相比，在将纳米颗粒重复注射到荷瘤裸鼠中后，更多的AuNP-EK10可能在肿瘤组织中积累，这对于癌症治疗中药物纳米载体的设计可能尤为重要。