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

IF 14.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
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
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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.

Abstract Image

设计一种高效、准确的近红外聚致发光材料用于dnazyme敏化光热治疗
基于聚集体诱导发射发光原(AIEgens)的光热疗法(PTT)已成为肿瘤消融的前沿领域。然而,由于经典AIEgens的光致发光(PL)和光热特性不协调,以及高温诱导的肿瘤细胞抗凋亡反应,阻碍了令人满意的治疗结果,挑战仍然存在。本文设计了一种近红外(NIR) spiro-AIEgen TTQ-SA,通过辅助dnazyme调节的肿瘤细胞致敏来提高PTT。初步制备出具有独特分子结构和封装方式的TTQ-SA,使其具有较强的AIE效应、良好的PL量子产率和良好的光热性能。DNAzyme作为基因沉默工具,可以缓解PTT的抗凋亡反应。通过将TTQ-SA和DNAzyme整合到叶酸修饰的聚乳酸-羟基乙酸(PLGA)聚合物中,制备的纳米系统可以促进细胞凋亡并使肿瘤细胞对PTT敏感,从而最大化治疗效果。该纳米系统结合spiro- aiegen为基础的PTT和dnazyme为基础的基因沉默,在肿瘤靶向方面显示出良好的近红外和光热成像能力,并对原位乳腺癌显示出显著的细胞凋亡、抗肿瘤和抗转移作用。此外,在自发的MMTV-PyMT转基因小鼠中实现了协同抗肿瘤作用。这些发现为基于aiegen的光热疗法和dnazyme调控的肿瘤细胞致敏提供了新的见解,为协同基因沉默- ptt纳米平台的临床研究铺平了道路。
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来源期刊
CiteScore
24.40
自引率
6.00%
发文量
2398
审稿时长
1.6 months
期刊介绍: The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.
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