Anti-plasma adhesion peptides from one-bead one-compound technique for drug delivery

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