Anti-Plasma Adhesion Peptides from One-Bead One-Compound Technique for Drug Delivery

Abstract

When the nanodrug enters the human body, it will inevitably encounter the blood, forming protein corona, which causes immune response, decreasing efficacy and losing targetability. In order to address this issue, we screened anti-adhesion peptides (AAPs) against the plasma by One-Bead One-Compound (OBOC) peptide library, and validated the advantages of the AAPs through modification of Asparaginase (ASP) as a representative nanodrug. The high plasma-stable and anti-adhesive peptides NLSNSPQ (AAP4) and KTENSPQ (AAP8) were optimized for modification of ASP to reduce immune response. ASP modified with one-layer AAP4 (ASP-AAP4-1), enzymatic activity remained 50.0% at 72 h after the third injection in mice, but ASP without modification remained less than 10.0%. Additionally, the IgG titer of anti-ASP antibodies for the ASP-AAP4-1 was decreased by 21 times, and the IgM titer decreased by 34 times. The screened peptide materials provide a promising anti-adhesion option for the efficient delivery of nanodrugs, or medical implants.