香港中文大学(深圳)医学院唐本忠团队报道了设计一种高效准确的近红外聚致发光材料，用于DNA酶敏化光热治疗。相关研究成果于2024年12月12日发表于国际一流学术期刊《美国化学会杂志》。

基于聚集诱导发射发光（AIEgens）的光热疗法（PTT）已成为肿瘤消融的前沿。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，因此仍然存在挑战。

该文设计了一种近红外（NIR）螺环-AIEgen-TTQ-SA，通过辅助DNA酶调节的肿瘤细胞致敏来增强PTT。初步制备了具有独特分子结构和堆积模式的TTQ-SA，使其具有很强的AIE效应、良好的PL量子产率和良好的光热性能。DNA酶作为一种基因沉默工具，可以缓解PTT过程中的抗凋亡反应。

通过将TTQ-SA和DNA酶整合到叶酸修饰的聚乳酸-羟基乙酸共聚物（PLGA）聚合物中，所制备的纳米系统可以促进细胞凋亡，使肿瘤细胞对PTT敏感，从而最大限度地提高治疗效果。

通过将基于螺体抗原的PTT和基于DNA酶的基因沉默相结合，设计的纳米系统显示出有希望的NIR和光热成像能力，用于肿瘤靶向，并对原位癌症表现出显著的细胞凋亡、抗肿瘤和抗转移作用。此外，在自发MMTV-PyMT转基因小鼠中实现了协同抗肿瘤作用。

研究发现为基于AIEgen的光热治疗，和DNA酶调节的肿瘤细胞致敏提供了新的见解，为临床研究中协同基因沉默PTT纳米平台铺平了道路。

附：英文原文

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

Author: 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

Issue&Volume: December 12, 2024

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.

DOI: 10.1021/jacs.4c14818

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c14818