TLD1433 Photosensitizer Inhibits Conjunctival Melanoma Cells in Zebrafish Ectopic and Orthotopic Tumour Models

Cancers
Quanchi ChenB Ewa Snaar-Jagalska

Abstract

The ruthenium-based photosensitizer (PS) TLD1433 has completed a phase I clinical trial for photodynamic therapy (PDT) treatment of bladder cancer. Here, we investigated a possible repurposing of this drug for treatment of conjunctival melanoma (CM). CM is a rare but often deadly ocular cancer. The efficacy of TLD1433 was tested on several cell lines from CM (CRMM1, CRMM2 and CM2005), uveal melanoma (OMM1, OMM2.5, MEL270), epidermoid carcinoma (A431) and cutaneous melanoma (A375). Using 15 min green light irradiation (21 mW/cm2, 19 J.cm-2, 520 nm), the highest phototherapeutic index (PI) was reached in CM cells, with cell death occurring via apoptosis and necrosis. The therapeutic potential of TLD1433 was hence further validated in zebrafish ectopic and newly-developed orthotopic CM models. Fluorescent CRMM1 and CRMM2 cells were injected into the circulation of zebrafish (ectopic model) or behind the eye (orthotopic model) and 24 h later, the engrafted embryos were treated with the maximally-tolerated dose of TLD1433. The drug was administrated in three ways, either by (i) incubating the fish in drug-containing water (WA), or (ii) injecting the drug intravenously into the fish (IV), or (iii) injecting the drug retro-orbitally (...Continue Reading

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Citations

Nov 18, 2020·Cancers·Ángeles JuarranzSalvador González
Mar 3, 2021·Chemical Communications : Chem Comm·Zhihui JinQianxiong Zhou
Mar 20, 2021·Chemical Science·Deborah A SmithenSherri A McFarland
Jun 15, 2021·Photochemistry and Photobiology·Chloe B SmithAlvin A Holder
Aug 18, 2021·European Journal of Medicinal Chemistry·Jiancheng MoRonny Priefer

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Methods Mentioned

BETA
xenograft
transgenic
fluorescence-activated cell sorting
fluorescence microscopy
confocal microscopy
fluorescence
FCS
FACS
Assay

Software Mentioned

ImageJ
Prism
GraphPad Prism
GraphPad
ZF4
Excel

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