A cascade FRET photosensitizer that enhances photodynamic therapy for ocular melanoma

A cascade FRET photosensitizer that enhances photodynamic therapy for ocular melanoma
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级联 FRET 光敏剂可增强眼部黑色素瘤的光动力治疗

DOI:
10.1016/j.nantod.2022.101684
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发表时间:
2022-12
期刊:
Nano Today (IF 18.962)
影响因子:
--
通讯作者:
Kam W. Leong
Kam W. Leong
中科院分区:
其他
文献类型:
--
作者:
Jing Ruan;Fang Li;Hao Tian;Jie Yu;Hongpei Deng;Shengfang Ge;Kam W. Leong

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Photodynamic therapy (PDT) relies on the generation of cytotoxic singlet oxygen (1O2) from an otherwise nontoxic photosensitizer accumulated in tumor tissue to treat cancer. However, PDT of uveal melanoma, the most common adult intraocular cancer, using potent porphyrin derivatives as photosensitizers has shown limited therapeutic efficacy due to low bioavailability and1O2yield. Here, considering the uveal melanoma microenvironment of endogenous melanin, which has a high absorption between 300 nm and 500 nm, we design a carbon dot-based photosensitizer that uses multiple different pathways to generate1O2. We conjugated gadolinium (Gd)-doped carbon dots (Gd@Cdots) with the porphyrin-derivatives chlorin e6 (Ce6) and verteporfin (Ver). The resulting nanoparticle (Gd@Cdots/Ce6/Ver) generates1O2under UV irradiation mainly in cascade FRET from Gd@Cdots to Ce6 and then to Ver; the photoactivated Ver, in turn, transfers its energy to3O2to generate1O2. In human uveal melanoma MUM-2B cells in vitro, Gd@Cdots/Ce6/Ver generated 7.1- and 2.4-fold higher production of hydroxyl radical (·OH) and superoxide anions (O2-·) following UV irradiation than Gd@Cdots, indicating greater induction of tumor cell apoptosis. In an orthotopic mouse model of uveal melanoma, PDT with Gd@Cdots/Ce6/Ver showed the same trend of superior potency in tumor growth inhibition. This photosensitizer design improves the PDT efficacy of uveal melanoma by enhancing the production of1O2and should be of broad utility to other PDT.
DOI: 10.3389/fchem.2015.00033
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影响因子: 5.5
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