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Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology

Photodynamic therapy (PDT) has become an effective treatment for certain types of solid tumors. The combination of PDT with other therapies has been extensively investigated in recent years to improve its effectiveness and expand its applications. This focused review summarizes the development of a...

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Autores principales: Nguyen, Luong, Li, Mengjie, Woo, Sukyung, You, Youngjae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947033/
https://www.ncbi.nlm.nih.gov/pubmed/31847080
http://dx.doi.org/10.3390/jcm8122198
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author Nguyen, Luong
Li, Mengjie
Woo, Sukyung
You, Youngjae
author_facet Nguyen, Luong
Li, Mengjie
Woo, Sukyung
You, Youngjae
author_sort Nguyen, Luong
collection PubMed
description Photodynamic therapy (PDT) has become an effective treatment for certain types of solid tumors. The combination of PDT with other therapies has been extensively investigated in recent years to improve its effectiveness and expand its applications. This focused review summarizes the development of a prodrug system in which anticancer drugs are activated locally at tumor sites during PDT treatment. The development of a singlet-oxygen-sensitive linker that can be conveniently conjugated to various drugs and efficiently cleaved to release intact drugs is recapitulated. The initial design of prodrugs, preliminary efficacy evaluation, pharmacokinetics study, and optimization using quantitative systems pharmacology is discussed. Current treatment optimization in animal models using physiologically based a pharmacokinetic (PBPK) modeling approach is also explored.
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spelling pubmed-69470332020-01-13 Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology Nguyen, Luong Li, Mengjie Woo, Sukyung You, Youngjae J Clin Med Review Photodynamic therapy (PDT) has become an effective treatment for certain types of solid tumors. The combination of PDT with other therapies has been extensively investigated in recent years to improve its effectiveness and expand its applications. This focused review summarizes the development of a prodrug system in which anticancer drugs are activated locally at tumor sites during PDT treatment. The development of a singlet-oxygen-sensitive linker that can be conveniently conjugated to various drugs and efficiently cleaved to release intact drugs is recapitulated. The initial design of prodrugs, preliminary efficacy evaluation, pharmacokinetics study, and optimization using quantitative systems pharmacology is discussed. Current treatment optimization in animal models using physiologically based a pharmacokinetic (PBPK) modeling approach is also explored. MDPI 2019-12-13 /pmc/articles/PMC6947033/ /pubmed/31847080 http://dx.doi.org/10.3390/jcm8122198 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Nguyen, Luong
Li, Mengjie
Woo, Sukyung
You, Youngjae
Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology
title Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology
title_full Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology
title_fullStr Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology
title_full_unstemmed Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology
title_short Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology
title_sort development of prodrugs for pdt-based combination therapy using a singlet-oxygen-sensitive linker and quantitative systems pharmacology
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947033/
https://www.ncbi.nlm.nih.gov/pubmed/31847080
http://dx.doi.org/10.3390/jcm8122198
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