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A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy

We report the self-assembly of amphiphilic BDQ photosensitizers into lysosome-targeting nanophotosensitizer BDQ-NP for highly effective photodynamic therapy (PDT). Molecular dynamics simulation, live cell imaging, and subcellular colocalization studies showed that BDQ strongly incorporated into lyso...

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Autores principales: Li, Youyou, Han, Wenbo, Gong, Deyan, Luo, Taokun, Fan, Yingjie, Mao, Jianming, Qin, Wenwu, Lin, Wenbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189857/
https://www.ncbi.nlm.nih.gov/pubmed/37206384
http://dx.doi.org/10.1039/d3sc00455d
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author Li, Youyou
Han, Wenbo
Gong, Deyan
Luo, Taokun
Fan, Yingjie
Mao, Jianming
Qin, Wenwu
Lin, Wenbin
author_facet Li, Youyou
Han, Wenbo
Gong, Deyan
Luo, Taokun
Fan, Yingjie
Mao, Jianming
Qin, Wenwu
Lin, Wenbin
author_sort Li, Youyou
collection PubMed
description We report the self-assembly of amphiphilic BDQ photosensitizers into lysosome-targeting nanophotosensitizer BDQ-NP for highly effective photodynamic therapy (PDT). Molecular dynamics simulation, live cell imaging, and subcellular colocalization studies showed that BDQ strongly incorporated into lysosome lipid bilayers to cause continuous lysosomal membrane permeabilization. Upon light irradiation, the BDQ-NP generated a high level of reactive oxygen species to disrupt lysosomal and mitochondrial functions, leading to exceptionally high cytotoxicity. The intravenously injected BDQ-NP accumulated in tumours to achieve excellent PDT efficacy on subcutaneous colorectal and orthotopic breast tumor models without causing systemic toxicity. BDQ-NP-mediated PDT also prevented metastasis of breast tumors to the lungs. This work shows that self-assembled nanoparticles from amphiphilic and organelle-specific photosensitizers provide an excellent strategy to enhance PDT.
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spelling pubmed-101898572023-05-18 A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy Li, Youyou Han, Wenbo Gong, Deyan Luo, Taokun Fan, Yingjie Mao, Jianming Qin, Wenwu Lin, Wenbin Chem Sci Chemistry We report the self-assembly of amphiphilic BDQ photosensitizers into lysosome-targeting nanophotosensitizer BDQ-NP for highly effective photodynamic therapy (PDT). Molecular dynamics simulation, live cell imaging, and subcellular colocalization studies showed that BDQ strongly incorporated into lysosome lipid bilayers to cause continuous lysosomal membrane permeabilization. Upon light irradiation, the BDQ-NP generated a high level of reactive oxygen species to disrupt lysosomal and mitochondrial functions, leading to exceptionally high cytotoxicity. The intravenously injected BDQ-NP accumulated in tumours to achieve excellent PDT efficacy on subcutaneous colorectal and orthotopic breast tumor models without causing systemic toxicity. BDQ-NP-mediated PDT also prevented metastasis of breast tumors to the lungs. This work shows that self-assembled nanoparticles from amphiphilic and organelle-specific photosensitizers provide an excellent strategy to enhance PDT. The Royal Society of Chemistry 2023-04-19 /pmc/articles/PMC10189857/ /pubmed/37206384 http://dx.doi.org/10.1039/d3sc00455d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Li, Youyou
Han, Wenbo
Gong, Deyan
Luo, Taokun
Fan, Yingjie
Mao, Jianming
Qin, Wenwu
Lin, Wenbin
A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy
title A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy
title_full A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy
title_fullStr A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy
title_full_unstemmed A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy
title_short A self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy
title_sort self-assembled nanophotosensitizer targets lysosomes and induces lysosomal membrane permeabilization to enhance photodynamic therapy
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189857/
https://www.ncbi.nlm.nih.gov/pubmed/37206384
http://dx.doi.org/10.1039/d3sc00455d
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