期刊
ADVANCED MATERIALS
卷 33, 期 32, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202100795
关键词
Ir(III) complexes; nanomedicine; photosensitizers; phototherapy; tumor ablation
类别
资金
- National Science Foundation [DMR-1411086]
- National Key R&D Program of China [2020YFA0710700]
- National Natural Science Foundation of China [51873143, 31771089, 31500811]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Suzhou Science and Technology Development Project [SS2019053, SYS2020083]
This study presents a neutral Ir(III) complex containing BODIPY-Ir that efficiently generates reactive oxygen species (ROS) and hyperthermia upon far-red light activation, enhancing in vivo tumor suppression through micellization. The complex completely destroys breast tumors and suppresses metastatic nodules under light irradiation, without significant dark cytotoxicity. This approach shows promise in developing potent cancer therapy using far-red/NIR photosensitizers.
A critical issue in photodynamic therapy (PDT) is inadequate reactive oxygen species (ROS) generation in tumors, causing inevitable survival of tumor cells that usually results in tumor recurrence and metastasis. Existing photosensitizers frequently suffer from relatively low light-to-ROS conversion efficiency with far-red/near-infrared (NIR) light excitation due to low-lying excited states that lead to rapid non-radiative decays. Here, a neutral Ir(III) complex bearing distyryl boron dipyrromethene (BODIPY-Ir) is reported to efficiently produce both ROS and hyperthermia upon far-red light activation for potentiating in vivo tumor suppression through micellization of BODIPY-Ir to form Micelle-Ir. BODIPY-Ir absorbs strongly at 550-750 nm with a band maximum at 685 nm, and possesses a long-lived triplet excited state with sufficient non-radiative decays. Upon micellization, BODIPY-Ir forms J-type aggregates within Micelle-Ir, which boosts both singlet oxygen generation and the photothermal effect through the high molar extinction coefficient and amplification of light-to-ROS/heat conversion, causing severe cell apoptosis. Bifunctional Micelle-Ir that accumulates in tumors completely destroys orthotopic 4T1 breast tumors via synergistic PDT/photothermal therapy (PTT) damage under light irradiation, and enables remarkable suppression of metastatic nodules in the lungs, together without significant dark cytotoxicity. The present study offers an emerging approach to develop far-red/NIR photosensitizers toward potent cancer therapy.
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