Ligand Engineering of Gold Nanoclusters for NIR-II Imaging

Abstract

Near-infrared-II (NIR-II) imaging has shown great potential in medical diagnosis and surgical navigation, but developing safe, photostable, high-brightness molecular probes remains a great challenge. Due to their ultrasmall size resulting in highly efficient renal clearance, gold nanoclusters have shown great clinical potential. In this work, we systematically explored the effect of different ligands on the luminescence and bioactivity of gold nanoclusters. Our results show that gold nanoclusters protected by thioglycolic acid (TGA) and 6-mercaptohexanoic acid (MHA) exhibit the strongest fluorescence, while 3mercaptopropionic acid (MPA)-and sodium sulfide (Na 2 S)-protected gold nanoclusters show the weakest NIR-II signal. Further doping showed that the Cd-doped MPA and MHA-protected gold nanoclusters exhibited enhanced fluorescence, but the cysteine (Cys)-, glutathione (GSH)-, and Na 2 S-protected gold nanoclusters showed fluorescence quenching after doping, indicating significant ligand selectivity. Because of the unique multi-energy structure and the large number of electronic states at the highest occupied molecular orbital energy level, MPA-and MHA-protected gold nanoclusters exhibit high stability and photostability. In addition, gold nanoclusters with different ligands exhibited different selective enzyme-mimicking activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT). Imaging in vivo showed that gold nanoclusters could accomplish reliable imaging of cerebral vasculature, hindlimb vessels, and spine as well as monitor renal clearance. The stable nanoclusters allow the time window of imaging to reach 125 min for hindlimb imaging and 270 min for spinal imaging. The gold nanoclusters exhibit a high signal-tonoise ratio of up to 11 for whole-body imaging and show efficient renal clearance and low toxicity at an injected dose of 50 mg/kg.

Enhanced brightness of ultra-small gold nanoparticles in the second biological window through thiol ligand shell control

“…The PL properties of the us-AuNPs exhibit a similar trend to that observed in other luminescent ultra-small NPs. 47 This trend involves a shift in PL towards longer wavelengths through the rigidification of the surface, which limits the access of water molecules to the gold surface and reduces non-radiative processes. 35 These findings are supported by the decrease in PL lifetime, indicating more efficient energy transfer to water molecule.…”

Chemical Flexibility of Atomically Precise Metal Clusters

“…Metal nanoclusters with limited metal atoms have the discrete electronic states related to quantum size effects, which are also regulated by the arrangement and numbers of metal atoms and diverse organic ligands. Such unique geometric and electric characteristics pose more unprecedented opportunities for them to display novel chemical-physical properties. , Examples of these properties include composition-dependent and size-dependent optical and electronic characteristics, − high emission spanning a broad spectrum from blue to the NIR II region, − enhanced electrical conductivity ,− and electrochemical activities, − magnetism, − intriguing chirality ,− and chiroptical activities (refs , , , , , , , and − ), and a high surface area-to-volume ratio that provides more active sites for catalytic reactions. ,,− …”

Gold Nanoclusters as High Resolution NIR-II Theranostic Agents

“…Possibility of renal clearance of AuNCs without any toxicological effects after 48 h was also revealed by their prominent presence in kidney. Further, Guo et al have used cadmium doped dual short thiol ligand (MHA = 6-mercaptohexanoic acid, MPA = 3-mercaptopropionic acid) protected gold nanoclusters (Au 7 Cd 1 -MHA/MPA) for the in vivo imaging of spine, hindlimb vessels, and cerebral vasculature . The prepared nanoclusters exhibited the potential for diagnosing and tracking brain vasculature disorders.…”

“…(D) Signal to noise ratio (SNR) of brain and leg vasculatures corresponding to (i) and (ii). Reproduced with permission from ref . Copyright 2023, American Chemical Society.…”