Intelligent gold nanocluster for effective treatment of malignant tumor via tumor-specific photothermal–chemodynamic therapy with AIE guidance

作者：Feng Liu, Tianfeng Yang, Xiaowei Chang, Li Chen, Cheng Cheng, Xiuhong Peng, Haihu Liu, Yanmin Zhang, Xin Chen · 发表于：National Science Review · 年份：2024 · DOI：10.1093/nsr/nwae113 · 被引用次数：19 · 研究领域：Nanoplatforms for cancer theranostics、Nanocluster Synthesis and Applications、Advanced Nanomaterials in Catalysis

ABSTRACT Precise and efficient therapy of malignant tumors is always a challenge. Herein, gold nanoclusters co-modified by aggregation-induced-emission (AIE) molecules, copper ion chelator (acylthiourea) and tumor-targeting agent (folic acid) were fabricated to perform AIE-guided and tumor-specific synergistic therapy with great spatio-temporal controllability for the targeted elimination and metastasis inhibition of malignant tumors. During therapy, the functional gold nanoclusters (AuNTF) would rapidly accumulate in the tumor tissue due to the enhanced permeability and retention effect as well as folic acid-mediated tumor targeting, which was followed by endocytosis by tumor cells. After that, the overexpressed copper ions in the tumor cells would trigger the aggregation of these intracellular AuNTF via a chelation process that not only generated the photothermal agent in situ to perform the tumor-specific photothermal therapy damaging the primary tumor, but also led to the copper deficiency of tumor cells to inhibit its metastasis. Moreover, the copper ions were reduced to cuprous ions along with the chelation, which further catalysed the excess H2O2 in the tumor cells to produce cytotoxic reactive oxygen species, resulting in additional chemodynamic therapy for enhanced antitumor efficiency. The aggregation of AuNTF also activated the AIE molecules to present fluorescence, which not only imaged the therapeutic area for real-time monitoring of this tumor-specific synergist...