Photodynamic therapy offers a novel approach to managing miltefosine-resistant cutaneous leishmaniasis
Date
08/2024Author
Grant ID
EP/R035164/1
EP/L015110/1
SFC/AN/12/2017
Keywords
Metadata
Show full item recordAbstract
Cutaneous leishmaniasis (CL) is a neglected disease caused by Leishmania parasites. The oral drug miltefosine is effective, but there is a growing problem of drug resistance, which has led to increasing treatment failure rates and relapse of infections. Photodynamic therapy (PDT) combines a light source and a photoactive drug to promote cell death by oxidative stress. Although PDT is effective against several pathogens, its use against drug resistant Leishmania parasites remains unexplored. Herein, we investigated the potential of organic light-emitting diodes (OLEDs) as wearable light sources, which would enable at-home use or ambulatory treatment of CL. We also assessed its impact on combating miltefosine resistance in Leishmania amazonensis-induced CL in mice. Thein vitro activity of OLEDs combined with 1,9-dimethyl-methylene blue (DMMB) (OLED-PDT) was evaluated against wild-type and miltefosine-resistant L. amazonensis strains in promastigote (EC50 = 0.034 μM for both strains) and amastigote forms (EC50 = 0.052 μM and 0.077 μM, respectively). Cytotoxicity in macrophages and fibroblasts was also evaluated. In vivo, we investigated the potential of OLED-PDT in combination with miltefosine using different protocols. Our results demonstrate that OLED-PDT is effective in killing both strains of L. amazonensis by increasing reactive oxygen species and stimulating nitric oxide production. Moreover, OLED-PDT showed great antileishmanial activity in vivo, allowing the reduction of miltefosine dose by half in infected mice using a light dose of 7.8 J/cm2 and 1.5 μM DMMB concentration. In conclusion, OLED-PDT emerges as a new avenue for at-home care and allows a combination therapy to overcome drug resistance in cutaneous leishmaniasis.
Citation
Cabral , F , Riahi , M , Persheyev , S , Lian , C , Cortez , M , Samuel , I D W & Ribeiro , M 2024 , ' Photodynamic therapy offers a novel approach to managing miltefosine-resistant cutaneous leishmaniasis ' , Biomedicine & Pharmacotherapy , vol. 177 , 116881 . https://doi.org/10.1016/j.biopha.2024.116881
Publication
Biomedicine & Pharmacotherapy
Status
Peer reviewed
ISSN
0753-3322Type
Journal article
Description
Funding: Engineering and Physical Sciences Research Council of the UK (grants EP/R035164/1 and EP/L015110/1) and the Scottish Funding Council (ODA GCRF fund grant SFC/AN/12/2017).Collections
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