An anionic and proline-rich peptide prolonged blood circulation of liposomes and evaded accelerated blood clearance after repeated administration.

In recent years, polypeptides have been standing out as excellent candidates to replace polyethylene glycol (PEG) with adequate biocompatibility and biodegradability. In this study, we found that (VELPPP)3, an anionic γ-zein-based proline-rich peptide with a polyproline-II helical structure, was able to impart liposomes with considerable stability and significantly prolonged blood circulation in vivo. Furthermore, we have shown that (VELPPP)3-modified liposomes induced negligible anti-peptide IgM production, and no noticeable accelerated blood clearance after repeated or multi-dose administration. The biodistribution study suggested that compared to PEGylated liposomes, (VELPPP)3-modified liposomes showed a slight inclination of accumulation in livers, and a decreased entrapment in most of the other organs over long hours. In conclusion, (VELPPP)3 has shown considerable capacity in establishing stealth nanocarriers, providing inspiring insights into developing alternatives for PEGylation.