Organotropic Engineering of Luminescent Gold Nanoclusters for In Vivo Imaging of Lung Orthotopic Tumors

Gold nanoclusters (AuNCs) are emerging as promising functional probes for bioapplications. However, because of rapid renal clearance, it is a challenge to tailor their biofate and improve their disease-targeting ability in vivo. Herein, we report an efficient strategy to tailor their organotropic actions by rationally designing AuNC assemblies. The nanocluster assembly is established based on the moderate electrostatic interaction or strong coordination between AuNCs, enabled by solely chitosan (CS) or the coadded chelating metal ions (e.g., Gd³⁺). We show that AuNCs-CS is rapidly excreted into urine, while further coordination of Gd³⁺ confers assemblies with liver and lung accumulation capabilities, dependent on Gd³⁺ contents. The organotropic actions are unraveled to result from their tunable stability in vivo and binding capability to cells/proteins. We also demonstrate that lung-targeting assemblies can enable specific NIR-II luminescence imaging of lung orthotopic tumors, which cannot be realized by employing discrete AuNCs. We anticipate that these findings will offer insights into the design principles of metal nanocluster probes and related bioapplications.