2. Academic Validation
  3. Pyridine-Embedded Phenothiazinium Dyes as Lysosome-Targeted Photosensitizers for Highly Efficient Photodynamic Antitumor Therapy

Pyridine-Embedded Phenothiazinium Dyes as Lysosome-Targeted Photosensitizers for Highly Efficient Photodynamic Antitumor Therapy

  • J Med Chem. 2020 May 14;63(9):4896-4907. doi: 10.1021/acs.jmedchem.0c00280.
Qicai Xiao 1 2,  Huirong Lin 3,  Juan Wu 2,  Xin Pang 2 3,  Quanming Zhou 1,  Yue Jiang 2,  Pan Wang 2,  Wingnang Leung 2,  Hungkay Lee 4,  Sheng Jiang 5,  Shao Q Yao 6,  Liqian Gao 1,  Gang Liu 3,  Chuanshan Xu 7 2
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China.
  • 2 School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China.
  • 3 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Centre for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
  • 4 Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, China.
  • 5 State Key Laboratory of Natural Medicines, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
  • 6 Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
  • 7 Key Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences & Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
PMID: 32267685 DOI: 10.1021/acs.jmedchem.0c00280
Abstract

Development of new photosensitizers (PSs) with high photodynamic efficacy and minimal side effects is of great interest in photodynamic therapy (PDT). In this work, we reported several pyridine-embedded phenothiazinium (pyridophenothiazinium) dyes, which could be conveniently synthesized in a few short steps and acted as highly efficient and potent PSs to selectively localize to lysosomes and photosensitively kill Cancer cells. Among them, compound 5, which possessed the ability of promoting intracellular Reactive Oxygen Species (ROS) upon light irradiation by almost 40-fold higher than that of methylene blue (MB, a general phenothiazinium-based PS), exhibited a remarkable phototherapeutic index (PI = 53.8) against HT29 Cancer cells, leading to eradication of large solid tumors (∼300 mm3) in a xenograft mouse model without apparent side effects. These results suggest that the pyridophenothiazinium dyes developed herein, especially compound 5, may serve as promising lysosome-targeted PSs for efficient photodynamic antitumor therapy.

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