科研之友
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摘要
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. @@@ We developed a smart surface mimic strategy for exogenous ultrasmall gold nanoparticles to construct protein mimics (P-AuNPs) and demonstrated that the P-AuNPs were identical to the endogenous filterable proteins not only in appearance but also in transcytosis-based tubular reabsorption. This surface-mimicking strategy can stimulate further investigation into many other endogenous metabolic pathways for exogenous substances.+ image
