Zwitterionic stealth peptide-protected gold nanoparticles enable long circulation without the accelerated blood clearance phenomenon.

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.