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Stimulus-responsive self-assembled prodrugs in cancer therapy

Small-molecule prodrugs have become the main toolbox to improve the unfavorable physicochemical properties of potential therapeutic compounds in contemporary anti-cancer drug development. Many approved small-molecule prodrugs, however, still face key challenges in their pharmacokinetic (PK) and phar...

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Autores principales: Dong, Xiao, Brahma, Rajeev K., Fang, Chao, Yao, Shao Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006903/
https://www.ncbi.nlm.nih.gov/pubmed/35509461
http://dx.doi.org/10.1039/d2sc01003h
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author Dong, Xiao
Brahma, Rajeev K.
Fang, Chao
Yao, Shao Q.
author_facet Dong, Xiao
Brahma, Rajeev K.
Fang, Chao
Yao, Shao Q.
author_sort Dong, Xiao
collection PubMed
description Small-molecule prodrugs have become the main toolbox to improve the unfavorable physicochemical properties of potential therapeutic compounds in contemporary anti-cancer drug development. Many approved small-molecule prodrugs, however, still face key challenges in their pharmacokinetic (PK) and pharmacodynamic (PD) properties, thus severely restricting their further clinical applications. Self-assembled prodrugs thus emerged as they could take advantage of key benefits in both prodrug design and nanomedicine, so as to maximize drug loading, reduce premature leakage, and improve PK/PD parameters and targeting ability. Notably, temporally and spatially controlled release of drugs at cancerous sites could be achieved by encoding various activable linkers that are sensitive to chemical or biological stimuli in the tumor microenvironment (TME). In this review, we have comprehensively summarized the recent progress made in the development of single/multiple-stimulus-responsive self-assembled prodrugs for mono- and combinatorial therapy. A special focus was placed on various prodrug conjugation strategies (polymer–drug conjugates, drug–drug conjugates, etc.) that facilitated the engineering of self-assembled prodrugs, and various linker chemistries that enabled selective controlled release of active drugs at tumor sites. Furthermore, some polymeric nano-prodrugs that entered clinical trials have also been elaborated here. Finally, we have discussed the bottlenecks in the field of prodrug nanoassembly and offered potential solutions to overcome them. We believe that this review will provide a comprehensive reference for the rational design of effective prodrug nanoassemblies that have clinic translation potential.
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spelling pubmed-90069032022-05-03 Stimulus-responsive self-assembled prodrugs in cancer therapy Dong, Xiao Brahma, Rajeev K. Fang, Chao Yao, Shao Q. Chem Sci Chemistry Small-molecule prodrugs have become the main toolbox to improve the unfavorable physicochemical properties of potential therapeutic compounds in contemporary anti-cancer drug development. Many approved small-molecule prodrugs, however, still face key challenges in their pharmacokinetic (PK) and pharmacodynamic (PD) properties, thus severely restricting their further clinical applications. Self-assembled prodrugs thus emerged as they could take advantage of key benefits in both prodrug design and nanomedicine, so as to maximize drug loading, reduce premature leakage, and improve PK/PD parameters and targeting ability. Notably, temporally and spatially controlled release of drugs at cancerous sites could be achieved by encoding various activable linkers that are sensitive to chemical or biological stimuli in the tumor microenvironment (TME). In this review, we have comprehensively summarized the recent progress made in the development of single/multiple-stimulus-responsive self-assembled prodrugs for mono- and combinatorial therapy. A special focus was placed on various prodrug conjugation strategies (polymer–drug conjugates, drug–drug conjugates, etc.) that facilitated the engineering of self-assembled prodrugs, and various linker chemistries that enabled selective controlled release of active drugs at tumor sites. Furthermore, some polymeric nano-prodrugs that entered clinical trials have also been elaborated here. Finally, we have discussed the bottlenecks in the field of prodrug nanoassembly and offered potential solutions to overcome them. We believe that this review will provide a comprehensive reference for the rational design of effective prodrug nanoassemblies that have clinic translation potential. The Royal Society of Chemistry 2022-03-18 /pmc/articles/PMC9006903/ /pubmed/35509461 http://dx.doi.org/10.1039/d2sc01003h Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Dong, Xiao
Brahma, Rajeev K.
Fang, Chao
Yao, Shao Q.
Stimulus-responsive self-assembled prodrugs in cancer therapy
title Stimulus-responsive self-assembled prodrugs in cancer therapy
title_full Stimulus-responsive self-assembled prodrugs in cancer therapy
title_fullStr Stimulus-responsive self-assembled prodrugs in cancer therapy
title_full_unstemmed Stimulus-responsive self-assembled prodrugs in cancer therapy
title_short Stimulus-responsive self-assembled prodrugs in cancer therapy
title_sort stimulus-responsive self-assembled prodrugs in cancer therapy
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006903/
https://www.ncbi.nlm.nih.gov/pubmed/35509461
http://dx.doi.org/10.1039/d2sc01003h
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