2. Academic Validation
  3. Engineering a Near-Infrared Spiro-Based Aggregation-Induced Emission Luminogen for DNAzyme-Sensitized Photothermal Therapy with High Efficiency and Accuracy

Engineering a Near-Infrared Spiro-Based Aggregation-Induced Emission Luminogen for DNAzyme-Sensitized Photothermal Therapy with High Efficiency and Accuracy

  • J Am Chem Soc. 2024 Dec 25;146(51):35462-35477. doi: 10.1021/jacs.4c14818.
Yingying Chen 1,  Sheng-Yi Yang 1,  Xinwen Ou 1,  Hui Wang 2,  Fan-Cheng Kong 3,  Philip C Y Chow 3,  Yifei Wang 2,  Yuqian Jiang 2,  Wei Zhao 1 4,  Jianwei Sun 1,  Ryan T K Kwok 1,  Di-Wei Zheng 5,  Wenqian Yu 2,  Fuan Wang 2,  Jacky W Y Lam 1,  Ben Zhong Tang 1 6
Affiliations

Affiliations

  • 1 Department of Chemistry, the Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemical and Biological Engineering, Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon 999077, Hong Kong SAR, China.
  • 2 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430071, China.
  • 3 Department of Mechanical Engineering, The University of Hong Kong, Pokfulam 999077, Hong Kong SAR, China.
  • 4 Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou City 510280, Guangdong, China.
  • 5 Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
  • 6 School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Shenzhen 518172, Guangdong, China.
PMID: 39665333 DOI: 10.1021/jacs.4c14818
Abstract

Aggregation-induced emission luminogen (AIEgens)-based photothermal therapy (PTT) has grown into a sparkling frontier for tumor ablation. However, challenges remain due to the uncoordinated photoluminescence (PL) and photothermal properties of classical AIEgens, along with hyperthermia-induced antiapoptotic responses in tumor cells, hindering satisfactory therapeutic outcomes. Herein, a near-infrared (NIR) spiro-AIEgen TTQ-SA was designed for boosted PTT by auxiliary DNAzyme-regulated tumor cell sensitization. TTQ-SA with a unique molecular structure and packing mode was initially fabricated, endowing it with a strong AIE effect, favorable PL quantum yield, and good photothermal performance. DNAzyme, as a gene silencing tool, could alleviate antiapoptosis response during PTT. By integrating TTQ-SA and DNAzyme into folate-modified poly(lactic-co-glycolic acid) (PLGA) polymer, the as-fabricated nanosystem could promote cell Apoptosis and sensitize tumor cells to PTT, thereby maximizing the therapeutic outcomes. With the combination of spiro-AIEgen-based PTT and DNAzyme-based gene silencing, the as-designed nanosystem showed promising NIR and photothermal imaging abilities for tumor targeting and demonstrated significant cell apoptotic, antitumor, and antimetastasis effects against orthotopic breast Cancer. Furthermore, a synergistic antitumor effect was realized in spontaneous MMTV-PyMT transgenic mice. These findings offer new insights into AIEgen-based photothermal theranostics and DNAzyme-regulated tumor cell sensitization, paving the way for synergistic gene silencing-PTT nanoplatforms in clinical research.

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