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.

中文翻译：

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智能金纳米簇通过 AIE 引导下的肿瘤特异性光热化学动力学疗法有效治疗恶性肿瘤

恶性肿瘤的精准、高效治疗始终是一个挑战。在此，制备了由聚集诱导发射（AIE）分子、铜离子螯合剂（酰基硫脲）和肿瘤靶向剂（叶酸）共同修饰的金纳米簇，以进行具有良好时空可控性的AIE引导和肿瘤特异性协同治疗用于恶性肿瘤的靶向消除和转移抑制。治疗过程中，功能性金纳米簇（AuNTF）由于渗透性和滞留效应增强以及叶酸介导的肿瘤靶向作用而在肿瘤组织中迅速积累，随后被肿瘤细胞内吞。之后，肿瘤细胞中过度表达的铜离子会通过螯合过程触发这些细胞内AuNTF的聚集，不仅原位产生光热剂，对原发肿瘤进行肿瘤特异性光热治疗，而且导致铜肿瘤细胞缺乏抑制其转移。此外，铜离子随着螯合被还原为亚铜离子，进一步催化肿瘤细胞中过量的H2O2产生细胞毒性ROS，从而进行额外的化学动力学治疗以增强抗肿瘤效率。 AuNTF的聚集还激活AIE分子呈现荧光，这不仅对治疗区域进行成像以实时监测这种肿瘤特异性协同治疗，而且使我们能够在适当的时间点和位置进行近红外辐射以实现最佳的光热治疗。体外和体内结果均表明，经 AuNTF 纳米团簇治疗后，荷瘤小鼠具有很强的肿瘤消除能力、有效的转移抑制能力和较高的存活率，表明这种 AIE 引导的肿瘤特异性协同策略可以为肿瘤治疗提供一种有前途的方法。肿瘤治疗。