Localized Instillation Enables <i>In Vivo</i> Screening of Targeting Peptides Using One-Bead One-Compound Technology.

Abstract

The One-Bead One-Compound (OBOC) library screening is an efficient technique for identifying targeting peptides. However, due to the relatively large bead size, it is challenging for the OBOC method to be applied for <i>in vivo</i> screening. Herein, we report an <i>in vivo</i> Localized Instillation Beads library (LIB) screening method to discover targeting peptides with the OBOC technique. Inspired by localized instillation, we constructed a cavity inside of a transplanted tumor of a mouse. Then, the OBOC heptapeptide library was injected and incubated inside the tumor cavity. After an efficient elution process, the retained beads were gathered, from which three MDA-MB-231 tumor-targeting heptapeptides were discovered. It was verified that the best peptide had 1.9-fold higher tumor accumulation than the commonly used targeting peptide RGD <i>in vivo</i>. Finally, two targeting proteins were discovered as potential targets of our targeting peptide to the MDA-MB-231 tumor. The <i>in vivo</i> LIB screening method expands the scope of OBOC peptide screening applications to discover targeting peptides <i>in vivo</i> feasibly and reliably.