Glutathione-responsive Aggregation-induced Emission Photosensitizers for Enhanced Photodynamic Therapy of Lung Cancer

被引:11
作者
Sun, Feiyi [1 ]
Chen, Yuyang [1 ,2 ]
Lam, Kristy W. K. [1 ]
Du, Wutong [1 ]
Liu, Qingqing [3 ]
Han, Fei [2 ]
Li, Dan [2 ]
Lam, Jacky W. Y. [1 ]
Sun, Jianwei [1 ]
Kwok, Ryan T. K. [1 ]
Tang, Ben Zhong [1 ,4 ]
机构
[1] Hong Kong Univ Sci & Technol, Chinese Natl Engn Res Ctr Tissue Restorat & Recon, Hong Kong Branch, Dept Chem,Kowloon, Clear Water Bay, Hong Kong 999077, Peoples R China
[2] Shenzhen Bay Lab, Inst Infect Dis, Shenzhen 518132, Peoples R China
[3] Univ Hong Kong, Li Ka Shing Fac Med, Sch Chinese Med, Pokfulam, Hong Kong 999077, Peoples R China
[4] Chinese Univ Hong Kong Shenzhen CUHK Shenzhen, Shenzhen Inst Aggregate Sci & Technol, Sch Sci & Engn, Shenzhen 518172, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
aggregation-induced emissions; glutathione; intersystem crossing; lung cancer; photodynamic therapy; FLUORESCENCE; MECHANISMS; ROS;
D O I
10.1002/smll.202401334
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Lung cancer, a highly prevalent and lethal form of cancer, is often associated with oxidative stress. Photodynamic therapy (PDT) has emerged as a promising alternative therapeutic tool in cancer treatments, but its efficacy is closely correlated to the photosensitizers generating reactive oxygen species (ROS) and the antioxidant capacity of tumor cells. In particular, glutathione (GSH) can reduce the ROS and thus compromise PDT efficacy. In this study, a GSH-responsive near-infrared photosensitizer (TBPPN) based on aggregation-induced emission for real-time monitoring of GSH levels and enhanced PDT for lung cancer treatment is developed. The strategic design of TBPPN, consisting of a donor-acceptor structure and incorporation of dinitrobenzene, enables dual functionality by not only the fluorescence being activated by GSH but also depleting GSH to enhance the cytotoxic effect of PDT. TBPPN demonstrates synergistic PDT efficacy in vitro against A549 lung cancer cells by specifically targeting different cellular compartments and depleting intracellular GSH. In vivo studies further confirm that TBPPN can effectively inhibit tumor growth in a mouse model with lung cancer, highlighting its potential as an integrated agent for the diagnosis and treatment of lung cancer. This approach enhances the effectiveness of PDT for lung cancer and deserves further exploration of its potential for clinical application.
引用
收藏
页数:12
相关论文
共 62 条
[1]   Photodynamic therapy to a primary cancer of the peripheral lung: Case report [J].
Allison, Ron R. ;
Ferguson, J. Scott .
PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY, 2022, 39
[2]   Current Advances in Photodynamic Therapy (PDT) and the Future Potential of PDT-Combinatorial Cancer Therapies [J].
Alvarez, Niuska ;
Sevilla, Ana .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (02)
[3]   Glutathione: new roles in redox signaling for an old antioxidant [J].
Aquilano, Katia ;
Baldelli, Sara ;
Ciriolo, Maria R. .
FRONTIERS IN PHARMACOLOGY, 2014, 5
[4]   Oxidative Stress in Cancer Cell Metabolism [J].
Arfin, Saniya ;
Jha, Niraj Kumar ;
Jha, Saurabh Kumar ;
Kesari, Kavindra Kumar ;
Ruokolainen, Janne ;
Roychoudhury, Shubhadeep ;
Rathi, Brijesh ;
Kumar, Dhruv .
ANTIOXIDANTS, 2021, 10 (05)
[5]  
Augustine R., 2020, Handbook of Biomaterials Biocompatibility, P473, DOI DOI 10.1016/B978-0-08-102967-1.00022-0
[6]   Photodynamic Therapy: Current Status and Future Directions [J].
Benov, Ludmil .
MEDICAL PRINCIPLES AND PRACTICE, 2015, 24 :14-28
[7]   Solvatochromic investigation of highly fluorescent 2-aminobithiophene derivatives [J].
Bolduc, Andreanne ;
Dong, Yanmei ;
Guerin, Amelie ;
Skene, W. G. .
PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 2012, 14 (19) :6946-6956
[8]   Mechanisms of Resistance to Photodynamic Therapy [J].
Casas, A. ;
Di Venosa, G. ;
Hasan, T. ;
Batlle, Al. .
CURRENT MEDICINAL CHEMISTRY, 2011, 18 (16) :2486-2515
[9]   Highly Efficient Near-Infrared Photosensitizers with Aggregation-Induced Emission Characteristics: Rational Molecular Design and Photodynamic Cancer Cell Ablation [J].
Chen, Dugang ;
Long, Zi ;
Zhong, Cheng ;
Chen, Li ;
Dang, Yecheng ;
Hu, Jing-Jing ;
Lou, Xiaoding ;
Xia, Fan .
ACS APPLIED BIO MATERIALS, 2021, 4 (06) :5231-5239
[10]   Fluorescent probes in public health and public safety [J].
Chu, Hao ;
Yang, Li ;
Yu, Le ;
Kim, Jungryun ;
Zhou, Jin ;
Li, Mingle ;
Kim, Jong Seung .
COORDINATION CHEMISTRY REVIEWS, 2021, 449