State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Taizhou Traditional Chinese Medicine Hospital, Taizhou, 318001, China.
Small. 2024 Nov;20(46):e2402854. doi: 10.1002/smll.202402854. Epub 2024 Aug 1.
Bacterial infections are closely correlated with the genesis and progression of cancer, and the elimination of cancer-related bacteria may improve the efficacy of cancer treatment. However, the combinatorial therapy that utilizes two or more chemodrugs will increase potential adverse effects. Image-guided photodynamic therapy is a highly precise and potential therapy to treat tumor and microbial infections. Herein, four donor-acceptor-π-bridge-acceptor (D-A-π-A) featured near-infrared (NIR) aggregation-induced emission luminogens (AIEgens) (TQTPy, TPQTPy, TQTC, and TPQTC) with type I and type II reaction oxygen species (ROS) generation capabilities are synthesized. Notably, TQTPy shows mitochondria targeted capacity, the best ROS production efficiency, long-term tumor retention capacity, and more importantly, the three-in-one fluorescence imaging guided therapy against both tumor and microbial infections. Both in vitro and in vivo results validate that TQTPy performs well in practical biomedical application in terms of NIR-fluorescence imaging-guided photodynamic cancer diagnosis and treatment. Moreover, the amphiphilic and positively charged TQTPy is able to specific and ultrafast discrimination and elimination of Gram-positive (G+) Staphylococcus aureus from Gram-negative (G-) Escherichia coli and normal cells. This investigation provides an instructive way for the construction of three-in-one treatment for image-guided photodynamic cancer therapy and bacteria elimination.
细菌感染与癌症的发生和发展密切相关,消除与癌症相关的细菌可能会提高癌症治疗的效果。然而,利用两种或更多种化疗药物的联合治疗会增加潜在的不良反应。影像引导的光动力疗法是一种高度精确且有潜力的治疗肿瘤和微生物感染的方法。本文合成了具有 I 型和 II 型活性氧(ROS)生成能力的四个供体-受体-π-桥-受体(D-A-π-A)近红外(NIR)聚集诱导发射发光体(AIEgens)(TQTPy、TPQTPy、TQTC 和 TPQTC)。值得注意的是,TQTPy 具有靶向线粒体的能力、最佳的 ROS 生成效率、长期的肿瘤保留能力,更重要的是,具有针对肿瘤和微生物感染的三合一荧光成像引导治疗的能力。体外和体内结果均验证了 TQTPy 在近红外荧光成像引导光动力癌症诊断和治疗的实际生物医学应用中表现良好。此外,两亲性和带正电荷的 TQTPy 能够特异性和超快地区分和消除革兰氏阳性(G+)金黄色葡萄球菌与革兰氏阴性(G-)大肠杆菌和正常细胞。这项研究为构建用于影像引导光动力癌症治疗和细菌消除的三合一治疗方法提供了一种有指导意义的方法。