Transcytosis‐Based Renal Tubular Reabsorption of Luminescent Gold Nanoparticles for Enhanced Tumor Imaging
Di Huang, Yue Tan, Jiahao Tang, Kui He, Yuxuan Zhou, Jinbin Liu
Abstract
Abstract Transcytosis‐based tubular reabsorption of endogenous proteins is a well‐known energy‐saving pathway that prevents nutrient loss. However, utilization of this well‐known reabsorption pathway for the delivery of exogenous nanodrugs remains a challenge. In this study, using the surface mimic strategy of a specific PEPT1/2‐targeted Gly−Sar peptide as a ligand, renal‐clearable luminescent gold nanoparticles (P−AuNPs) were developed as protein mimics to investigate the transcytosis‐based tubular reabsorption of exogenous substances. By regulating the influential factors (H + content in tubular lumens and PEPT1/2 transporter counts in tubular cells) of Gly−Sar‐mediated transcytosis, the specific and efficient interaction between P−AuNPs and renal tubular cells was demonstrated both in vitro and in vivo. Efficient transcellular transportation significantly guided the reabsorption of P−AuNPs back into the bloodstream, which enhanced the blood concentration and bioavailability of nanoparticles, contributing to high‐contrast tumor imaging.