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Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy

Elevated cathepsins levels and activities are found in several types of human cancer, making them valuable biomarkers for detection and targeting therapeutics. We designed small molecule quenched activity-based probes (qABPs) that fluoresce upon activity-dependent covalent modification, yielding cel...

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Autores principales: Ben-Nun, Yael, Merquiol, Emmanuelle, Brandis, Alexander, Turk, Boris, Scherz, Avigdor, Blum, Galia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440442/
https://www.ncbi.nlm.nih.gov/pubmed/26000057
http://dx.doi.org/10.7150/thno.10854
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author Ben-Nun, Yael
Merquiol, Emmanuelle
Brandis, Alexander
Turk, Boris
Scherz, Avigdor
Blum, Galia
author_facet Ben-Nun, Yael
Merquiol, Emmanuelle
Brandis, Alexander
Turk, Boris
Scherz, Avigdor
Blum, Galia
author_sort Ben-Nun, Yael
collection PubMed
description Elevated cathepsins levels and activities are found in several types of human cancer, making them valuable biomarkers for detection and targeting therapeutics. We designed small molecule quenched activity-based probes (qABPs) that fluoresce upon activity-dependent covalent modification, yielding cell killing by Photodynamic Therapy (PDT). These novel molecules are highly selective theranostic probes that enable both detection and treatment of cancer with minimal side effects. Our qABPs carry a photosensitizer (PS), which is activated by light, resulting in oxidative stress and subsequent cell ablation, and a quencher that when removed by active cathepsins allow the PS to fluoresce and demonstrate PD properties. Our most powerful and stable PS-qABP, YBN14, consists of a selective cathepsin recognition sequence, a QC-1 quencher and a new bacteriochlorin derivative as a PS. YBN14 allowed rapid and selective non-invasive in vivo imaging of subcutaneous tumors and induced specific tumor macrophage apoptosis by light treatment, resulting in a substantial tumor shrinkage in an aggressive breast cancer mouse model. These results demonstrate for the first time that the PS-qABPs technology offers a functional theranostic tool, which can be applied to numerous tumor types and other inflammation-associated diseases.
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spelling pubmed-44404422015-05-21 Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy Ben-Nun, Yael Merquiol, Emmanuelle Brandis, Alexander Turk, Boris Scherz, Avigdor Blum, Galia Theranostics Research Paper Elevated cathepsins levels and activities are found in several types of human cancer, making them valuable biomarkers for detection and targeting therapeutics. We designed small molecule quenched activity-based probes (qABPs) that fluoresce upon activity-dependent covalent modification, yielding cell killing by Photodynamic Therapy (PDT). These novel molecules are highly selective theranostic probes that enable both detection and treatment of cancer with minimal side effects. Our qABPs carry a photosensitizer (PS), which is activated by light, resulting in oxidative stress and subsequent cell ablation, and a quencher that when removed by active cathepsins allow the PS to fluoresce and demonstrate PD properties. Our most powerful and stable PS-qABP, YBN14, consists of a selective cathepsin recognition sequence, a QC-1 quencher and a new bacteriochlorin derivative as a PS. YBN14 allowed rapid and selective non-invasive in vivo imaging of subcutaneous tumors and induced specific tumor macrophage apoptosis by light treatment, resulting in a substantial tumor shrinkage in an aggressive breast cancer mouse model. These results demonstrate for the first time that the PS-qABPs technology offers a functional theranostic tool, which can be applied to numerous tumor types and other inflammation-associated diseases. Ivyspring International Publisher 2015-04-27 /pmc/articles/PMC4440442/ /pubmed/26000057 http://dx.doi.org/10.7150/thno.10854 Text en © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Ben-Nun, Yael
Merquiol, Emmanuelle
Brandis, Alexander
Turk, Boris
Scherz, Avigdor
Blum, Galia
Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy
title Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy
title_full Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy
title_fullStr Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy
title_full_unstemmed Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy
title_short Photodynamic Quenched Cathepsin Activity Based Probes for Cancer Detection and Macrophage Targeted Therapy
title_sort photodynamic quenched cathepsin activity based probes for cancer detection and macrophage targeted therapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440442/
https://www.ncbi.nlm.nih.gov/pubmed/26000057
http://dx.doi.org/10.7150/thno.10854
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