Liu Feng, Yang Tianfeng, Chang Xiaowei, Chen Li, Cheng Cheng, Peng Xiuhong, Liu Haihu, Zhang Yanmin, Chen Xin
School of Energy and Power Engineering, Xi'an Jiaotong University, Xi'an 710049, China.
Department of Chemical Engineering, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, School of Chemical Engineering and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
Natl Sci Rev. 2024 Mar 22;11(5):nwae113. doi: 10.1093/nsr/nwae113. eCollection 2024 May.
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 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 HO 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 synergistic therapy, but also allowed us to perform near-infrared radiation at the correct time point and location to achieve optimal photothermal therapy. Both and results revealed the strong tumor elimination, effective metastasis inhibition and high survival rate of tumor-bearing mice after treatment using the AuNTF nanoclusters, indicating that this AIE-guided and tumor-specific synergistic strategy could offer a promising approach for tumor therapy.
恶性肿瘤的精准高效治疗一直是一项挑战。在此，制备了由聚集诱导发光（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，以实现具有良好时空可控性的AIE引导的肿瘤特异性协同治疗，用于靶向消除和抑制恶性肿瘤转移。在治疗过程中，功能性金纳米簇（AuNTF）由于增强的渗透和滞留效应以及叶酸介导的肿瘤靶向作用，会迅速在肿瘤组织中积累，随后被肿瘤细胞内吞。之后，肿瘤细胞中过表达的铜离子会通过螯合过程触发这些细胞内AuNTF的聚集，这不仅产生光热剂以进行肿瘤特异性光热治疗来损伤原发肿瘤，还会导致肿瘤细胞铜缺乏以抑制其转移。此外，随着螯合作用，铜离子被还原为亚铜离子，进一步催化肿瘤细胞中过量的羟基自由基产生细胞毒性活性氧，从而实现额外的化学动力治疗以提高抗肿瘤效率。AuNTF的聚集还激活了AIE分子以呈现荧光，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，还使我们能够在正确的时间点和位置进行近红外辐射以实现最佳光热治疗。体内和体外结果均显示，使用AuNTF纳米簇治疗后，荷瘤小鼠具有强大的肿瘤消除能力、有效的转移抑制作用和高生存率，表明这种AIE引导的肿瘤特异性协同策略可为肿瘤治疗提供一种有前景的方法。
