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

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

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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 synergistic therapy,but also allowed us to perform near-infrared radiation at the correct 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 using the AuNTF nanoclusters,indicating that this AIE-guided and tumor-specific synergistic strategy could offer a promising approach for tumor therapy.

AIE-guided precise tumor treatmentcopper-dependent photothermal therapycopper-triggered chemodynamic therapyprimary tumor eliminationcopper-plunder-induced metastasis inhibition

Feng Liu、Tianfeng Yang、Xiaowei Chang、Li Chen、Cheng Cheng、Xiuhong Peng、Haihu Liu、Yanmin Zhang、Xin Chen

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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

School of Pharmacy,Health Science Center,Xi'an Jiaotong University,Xi'an 710061,China

National High Level Talents Special Support Plan国家自然科学基金the'Young Talent Support Plan'of Xi'an Jiaotong UniversityShaanxi Innovative Research Team of Science and Technology陕西省自然科学基金国家重点研发计划

82272141S2023-ZC-TD-01522022JZ-482023YFC2509104

2024

10.1093/nsr/nwae113

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ISSN：
年,卷(期)：2024.11(5)
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