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

Abstract

Precise and efficient therapy of malignant tumor is always a challenge. Herein, gold nanoclusters co-modified by aggregation-induced-emission (AIE) molecules, copper ions chelator (acylthiourea) and tumor targeting agent (folic acid) were fabricated to perform the AIE-guided and tumor-specific synergistic therapy with great spatiotemporal controllability for the targeted elimination and metastasis inhibition of malignant tumor. During therapy, the functional gold nanoclusters (AuNTF) would rapidly accumulate in tumor tissue due to the enhanced permeability and retention effect as well as folic acid mediated tumor targeting, which was followed with the endocytosis by tumor cells. After that, the over-expressed copper ions in tumor cells would trigger the aggregation of these intracellular AuNTF via chelation process, which not only generated the photothermal agent in situ to perform the tumor-specific photothermal therapy damaging primary tumor, but 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 catalyzed the excess H2O2 in tumor cells to produce cytotoxic ROS, resulting in additional chemodynamic therapy for enhanced anti-tumor 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 synergistic therapy, but allowed us to perform NIR radiation at proper time point and location to achieve optimal photothermal therapy. Both in vitro and in vivo results revealed the strong tumor elimination, effective metastasis inhibition and high survival rate of tumor-bearing mice after treatment by the AuNTF nanoclusters, indicating that this AIE-guided and tumor-specific synergistic strategy could offer a promising approach for tumor therapy.