Journal
NANO TODAY
Volume 47, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2022.101684
Keywords
Uveal melanoma; Photodynamic therapy (PDT); Photosensitizer; Porphyrin derivatives; Cascade FRET; Singlet oxygen (O-1(2))
Categories
Funding
- National Natural Science Foundation of China [81972530, U1932135]
- Shanghai Pujiang Program [21PJD036]
- Fund for Excellent Young Scholars of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine [JYYQ001]
- China Scholarship Council [201906235030]
- Shanghai Rising-Star Program [17QA1402000]
- Science and Technology Commission of Shanghai [20DZ2270800]
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This study presents a carbon dot-based photosensitizer that generates cytotoxic singlet oxygen (O-1(2)) through multiple pathways, improving the therapeutic efficacy of photodynamic therapy (PDT) for uveal melanoma.
Photodynamic therapy (PDT) relies on the generation of cytotoxic singlet oxygen (O-1(2)) 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 and O-1(2) yield. 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 generate O-1(2). 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) generates O-1(2) under UV irradiation mainly in cascade FRET from Gd@Cdots to Ce6 and then to Ver; the photoactivated Ver, in turn, transfers its energy to O-3(2) to generate O-1(2). 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 (middotOH) and superoxide anions (O(2)(-)middot) 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 of O-1(2) and should be of broad utility to other PDT. (C) 2022 Elsevier Ltd. All rights reserved.
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