Anti-PEG scFv corona ameliorates accelerated blood clearance phenomenon of PEGylated nanomedicines

Anti-PEG antibodies have been witnessed in patients and experimental animals, accelerating the blood clearance (termed ABC phenomenon) of PEGylated nanomedicines by activating complement after absorption on the nano-surface. The ABC phenomenon presents an obstacle to the clinical translation of PEGylated nanomedicines. Herein, an anti-PEG single-chain variable fragment (PEG-scFv) that possesses a low molecule weight (30 kDa) and high PEG binding affinity was exploited to ameliorate the ABC phenomenon of PEGylated liposomes (sLip). Pre-deposition of PEG-scFv on the surface of sLip was incompetent to activate complement due to the lack of Fc chains, exhibiting negligible influence on in vivo performance of sLip in naïve rats (without anti-PEG antibodies). However, PEG-scFv effectively competed the binding of anti-PEG IgM in rats that were pre-stimulated with low dose of sLip, thus ameliorated the ABC phenomenon of sLip. PEG- scFv was also effective to inhibit the binding of anti-PEG antibodies with sLip in human plasma and the consequent complement activation, presenting a promising tool to improve the performance of PEGylated nanomedicines and to mitigate individual difference occurred by the varying levels of anti-PEG antibodies in the clinic. The application of anti-PEG scFv paves a new avenue for the development of nanocarriers to achieve precise medication.