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

• DOI: 10.1021/jacs.4c14818
• Publication Date: 2024-12-12T11:52:35Z
• Authors: Yingying Chen; Sheng-Yi Yang; Xinwen Ou; Hui Wang; Fan-Cheng Kong; Philip C. Y. Chow; Yifei Wang; Yuqian Jiang; Wei Zhao; Jianwei Sun; Ryan T. K. Kwok; Di-Wei Zheng; Wenqian Yu; Fuan Wang; Jacky W. Y. Lam; Ben Zhong Tang

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