pH-sensitive gold nanoclusters labeling with radiometallic nuclides for diagnosis and treatment of tumor
Yifei Jiang, Qinghe Wu, Mengfei Hou, Wangxi Hai, Min Zhang, Biao Li, Chunfu Zhang
Abstract
The acidic microenvironment is one of the remarkable features of tumor and is also a reliable target for tumor theranostics. Ultrasmall gold nanoclusters (AuNCs) have good in vivo behaviors, such as non-retention in liver and spleen, renal clearance, and high tumor permeability, and held great potential for developing novel radiopharmaceuticals. Herein, we developed pH-sensitive ultrasmall gold nanoclusters by introducing quaternary ammonium group (TMA) or tertiary amine motifs (C6A) onto glutathione-coated AuNCs (TMA/[email protected], [email protected]). Density functional theory simulation revealed that radiometal 89Sr, 223Ra, 44Sc, 90Y, 177Lu, 89Zr, 99mTc, 188Re, 106Rh, 64Cu, 68Ga, and 113Sn could stably dope into AuNCs. Both TMA/[email protected] and [email protected] could assemble into large clusters responding to mild acid condition, with [email protected] being more effective. To assess their performance for tumor detection and therapy, TMA/[email protected] and [email protected] were labeled with 68Ga, 64Cu, 89Zr and 89Sr, respectively. PET imaging of 4T1 tumor-bearing mice revealed TMA/[email protected] and [email protected] were mainly cleared through kidney, and [email protected] accumulated in tumors more efficiently. As a result, 89Sr-labeled [email protected] eradicated both the primary tumors and their lung metastases. Therefore, our study suggested that GSH-coated AuNCs held great promise for developing novel radiopharmaceuticals that specifically target the tumor acidic microenvironment for tumor diagnosis and treatments.