Carboxylesterase-Cleavable Biotinylated Nanoparticle for Tumor-Dual Targeted Imaging

Abstract

Near-infrared (NIR) nanoprobes with fluorescence "Turn-On" property are advantageous in cancer diagnosis but, to the best of our knowledge, "smart" nanoprobe that simultaneously targets both biotin receptor and carboxylesterase (CES) for HepG2 tumor-dual targeted imaging has not been reported. <b>Methods</b>: Using CBT-Cys click condensation reaction, we rationally designed a "smart" NIR fluorescence probe H₂N-Cys(StBu)-Lys(Biotin)-Ser(Cy5.5)-CBT (<b>NIR-CBT</b>) and used it to facilely prepare the fluorescence-quenched nanoparticle <b>NIR-CBT-NP</b>. <b>Results</b>: <i>In vitro</i> results indicated that, after <b>NIR-CBT-NP</b> was incubated with CES for 6 h, its fluorescence was turned "On" by 69 folds. Cell experiments verified that <b>NIR-CBT-NP</b> was uptaken by HepG2 cells <i>via</i> biotin receptor-assisted endocytosis and its fluorescence was turned "On" by intracellular CES hydrolysis. Moreover, <b>NIR-CBT-NP</b> was successfully applied to image both biotin receptor- and CES-overexpressing HepG2 tumors. <b>Conclusion</b>: Fluorescence-quenched nanoparticle <b>NIR-CBT-NP</b> was facilely prepared to actively target biotin receptor-overexpressing HepG2 cancer cells and turn the fluorescence "On" by intracellular CES hydrolysis for tumor-dual targeted imaging. We anticipate that our fluorescence "Turn-On" nanoparticle could be applied for liver cancer diagnosis in clinic in the near future.