Towards precision medicine using biochemically triggered cleavable conjugation

Abstract Personalised and precision medicines are emerging as the future of therapeutic strategies. Biochemically triggered cleavable conjugation is thus crucial and timely due to its potential to response as per the loco-regional environment. It enables targeted release of therapeutic agents in res...

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Main Authors: Badri Parshad, Smriti Arora, Balram Singh, Yuanwei Pan, Jianbin Tang, Zhigang Hu, Hirak K. Patra
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-025-01491-5
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author Badri Parshad
Smriti Arora
Balram Singh
Yuanwei Pan
Jianbin Tang
Zhigang Hu
Hirak K. Patra
author_facet Badri Parshad
Smriti Arora
Balram Singh
Yuanwei Pan
Jianbin Tang
Zhigang Hu
Hirak K. Patra
author_sort Badri Parshad
collection DOAJ
description Abstract Personalised and precision medicines are emerging as the future of therapeutic strategies. Biochemically triggered cleavable conjugation is thus crucial and timely due to its potential to response as per the loco-regional environment. It enables targeted release of therapeutic agents in response to specific biochemical signals and thus minimizing off-target effects and improving treatment precision. It holds promise in a range of biomedical applications, including cancer therapy, senolytic therapy, gene therapy, and regenerative medicine. The focus of this review is to offer comprehensive insight into the significance of biochemically cleavable conjugations within intrinsically stimuli-responsive architectures. Pathological conditions and alteration in tissues microenvironment in the body exhibit distinct biochemical settings characterized by change in redox potential, pH level, hypoxia, reactive oxygen species (ROS), and various catalytic protein/enzyme overexpression. Understanding these intrinsic features is crucial for researchers aiming to develop intelligent cleavable bio-engineered systems for biomedicines. By strategically designing cleavable linkage, researchers can leverage the variations in the tumor, infection, inflammation, and senescence microenvironments. Through an extensive examination of relevant literature, we present a comprehensive classification of the intrinsic physicochemical differences found in pathological areas and their applications in drug delivery, prodrug activation, imaging, and theranostics for future personalised medicines. This review will provide comprehensive guidance and critical insights to researchers in both industry and academia who are involved in the design of advanced, functional biochemically cleavable conjugations.
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spelling doaj-art-cc654a4ba4de41e8acfd9dd95419e6ef2025-08-20T03:08:05ZengNature PortfolioCommunications Chemistry2399-36692025-04-018111610.1038/s42004-025-01491-5Towards precision medicine using biochemically triggered cleavable conjugationBadri Parshad0Smriti Arora1Balram Singh2Yuanwei Pan3Jianbin Tang4Zhigang Hu5Hirak K. Patra6Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical SchoolInstitut für Chemie und Biochemie Organische Chemie, Freie Universität Berlin, Takustr. 3Faculty of Science and Engineering, Swansea UniversityInstitute of Biomedical Health Technology and Engineering, Shenzhen Bay LaboratoryZhejiang Key Laboratory of Smart Biomaterials and College of Chemical and Biological Engineering, Zhejiang UniversityCenter for Hydrogen Science, School of Material Science and Engineering, Shanghai Jiao Tong UniversityDepartment of Surgical Biotechnology, UCL Division of Surgery and Interventional Science, University College LondonAbstract Personalised and precision medicines are emerging as the future of therapeutic strategies. Biochemically triggered cleavable conjugation is thus crucial and timely due to its potential to response as per the loco-regional environment. It enables targeted release of therapeutic agents in response to specific biochemical signals and thus minimizing off-target effects and improving treatment precision. It holds promise in a range of biomedical applications, including cancer therapy, senolytic therapy, gene therapy, and regenerative medicine. The focus of this review is to offer comprehensive insight into the significance of biochemically cleavable conjugations within intrinsically stimuli-responsive architectures. Pathological conditions and alteration in tissues microenvironment in the body exhibit distinct biochemical settings characterized by change in redox potential, pH level, hypoxia, reactive oxygen species (ROS), and various catalytic protein/enzyme overexpression. Understanding these intrinsic features is crucial for researchers aiming to develop intelligent cleavable bio-engineered systems for biomedicines. By strategically designing cleavable linkage, researchers can leverage the variations in the tumor, infection, inflammation, and senescence microenvironments. Through an extensive examination of relevant literature, we present a comprehensive classification of the intrinsic physicochemical differences found in pathological areas and their applications in drug delivery, prodrug activation, imaging, and theranostics for future personalised medicines. This review will provide comprehensive guidance and critical insights to researchers in both industry and academia who are involved in the design of advanced, functional biochemically cleavable conjugations.https://doi.org/10.1038/s42004-025-01491-5
spellingShingle Badri Parshad
Smriti Arora
Balram Singh
Yuanwei Pan
Jianbin Tang
Zhigang Hu
Hirak K. Patra
Towards precision medicine using biochemically triggered cleavable conjugation
Communications Chemistry
title Towards precision medicine using biochemically triggered cleavable conjugation
title_full Towards precision medicine using biochemically triggered cleavable conjugation
title_fullStr Towards precision medicine using biochemically triggered cleavable conjugation
title_full_unstemmed Towards precision medicine using biochemically triggered cleavable conjugation
title_short Towards precision medicine using biochemically triggered cleavable conjugation
title_sort towards precision medicine using biochemically triggered cleavable conjugation
url https://doi.org/10.1038/s42004-025-01491-5
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