Abstract 2522: N-heterocyclic carbene (NHC)-protected gold nanoclusters for cancer imaging and therapy
Authors: Juan Chen, Elham Zeinizade, Viveka K. Kulkarni, Angus I. Sullivan, Brian C. Wilson, Marianne Koritzinsky, Cathleen M. Crudden, Gang Zheng
Journal: Cancer Research (2025)

Gold nanoclusters (AuNCs), commonly stabilized by thiol groups, hold significant promise for cancer theranostics, where their small size enables efficient renal clearance, and their atomically precise structures offer potential for drug-like properties [1-2]. N-heterocyclic carbene (NHC) ligands further enhance the versatility of AuNCs, introducing unique cluster compositions and improved stability [3]. Recently, NHC-protected AuNCs have emerged as tunable, emissive platforms with exceptional stability and photoluminescence, making them ideal candidates for applications in fluorescence imaging and photodynamic therapy [4]. In our work, we synthesized ultra-small bis-NHC-protected Au13 nanoclusters with π-extended aromatic systems, observing a correlation between increased structural rigidity and both high fluorescence quantum yield (57%) and reactive oxygen species (ROS) production efficiency (7%). Extensive stability and photophysical characterizations confirmed long emission lifetimes and high optical purity, with these nanoclusters maintaining robust stability and showing low toxicity under physiological conditions. Confocal microscopy and ICP-MS analyses verified effective cellular uptake across various cancer cell lines, and upon light activation, the nanoclusters functioned as potent photodynamic therapy agents, selectively inducing cancer cell destruction. PEGylation significantly improved water solubility and biocompatibility while maintaining photonic properties. Additionally, azide functionalization on cluster wings enabled targeted ligand attachment via click chemistry, demonstrated with folate receptor-mediated targeting for cancer imaging. With high stability, superior photoluminescence quantum yield, efficient cellular uptake, and clickable framework, these NHC-AuNCs provide a versatile and powerful nanoplatform for advanced cancer imaging and targeted therapy. References1. Huang, Y etc., Nat. Nanotechnol. 2023, 18 (6), 637-646. 2. Zhang, X.-D. etc., Enhanced Tumor Accumulation of Sub-2 Nm Gold Nanoclusters for Cancer Radiation Therapy. Advanced Healthcare Materials 2014, 3 (1), 133-141.3. Shen, H.; Tian, G.; Xu, Z.; Wang, L.; Wu, Q.; Zhang, Y.; Teo, B. K.; Zheng, N. etc., N-Heterocyclic Carbene Coordinated Metal Nanoparticles and Nanoclusters. Coordination Chemistry Reviews 2022, 458, 214425. 4. Albright, E. L. etc., N-Heterocyclic Carbene-Stabilized Atomically Precise Metal Nanoclusters. J. Am. Chem. Soc. 2024, 146 (9), 5759-5780. Citation Format: Juan Chen, Elham Zeinizade, Viveka K. Kulkarni, Angus I. Sullivan, Brian C. Wilson, Marianne Koritzinsky, Cathleen M. Crudden, Gang Zheng. N-heterocyclic carbene (NHC)-protected gold nanoclusters for cancer imaging and therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2522.