The design of small-molecule prodrugs and activatable phototherapeutics for cancer therapy
Cancer remains as one of the most significant health problems, with approximately 19 million people diagnosed worldwide each year. Chemotherapy is a routinely used method to treat cancer patients. However, current treatment options lack the appropriate selectivity for cancer cells, are prone to resi...
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| Published in | Chemical Society reviews Vol. 52; no. 3; pp. 879 - 92 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Royal Society of Chemistry
06.02.2023
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| Subjects | |
| Online Access | Get full text |
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| Summary: | Cancer remains as one of the most significant health problems, with approximately 19 million people diagnosed worldwide each year. Chemotherapy is a routinely used method to treat cancer patients. However, current treatment options lack the appropriate selectivity for cancer cells, are prone to resistance mechanisms, and are plagued with dose-limiting toxicities. As such, researchers have devoted their attention to developing prodrug-based strategies that have the potential to overcome these limitations. This tutorial review highlights recently developed prodrug strategies for cancer therapy. Prodrug examples that provide an integrated diagnostic (fluorescent, photoacoustic, and magnetic resonance imaging) response, which are referred to as theranostics, are also discussed. Owing to the non-invasive nature of light (and X-rays), we have discussed external excitation prodrug strategies as well as examples of activatable photosensitizers that enhance the precision of photodynamic therapy/photothermal therapy. Activatable photosensitizers/photothermal agents can be seen as analogous to prodrugs, with their phototherapeutic properties at a specific wavelength activated in the presence of disease-related biomarkers. We discuss each design strategy and illustrate the importance of targeting biomarkers specific to the tumour microenvironment and biomarkers that are known to be overexpressed within cancer cells. Moreover, we discuss the advantages of each approach and highlight their inherent limitations. We hope in doing so, the reader will appreciate the current challenges and available opportunities in the field and inspire subsequent generations to pursue this crucial area of cancer research.
This tutorial review provides a general overview for the design of prodrugs and activatable phototherapeutics which enables the development of improved therapies. |
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| Bibliography: | Jong Seung Kim (Left) received his PhD from the Department of Chemistry and Biochemistry at Texas Tech University in 1993. Currently he is a full professor in the Department of Chemistry at Korea University in Seoul. Mingle Li (Right) obtained his PhD degree in 2019 from the Dalian University of Technology under the supervision of Prof. Xiaojun Peng. Currently he is a Research Professor in Prof. Jong Seung Kim's lab at Korea University in Seoul. Han-Min Wang is currently pursuing a PhD degree at SIMM (CAS) with Prof. Yi Zang. Her research focuses on the biological research of new target for NASH treatment and development of new chemical probe tools for monitoring the development of NASH. Jia Li received his PhD from SIMM (CAS) in 2000 and was promoted to professor in 2005. He has been the director of SIMM (CAS) since 2019. His research interests are centered on the investigation of mechanisms of metabolic diseases and medicinal chemical biology. Paramesh Jangili received his PhD in 2016 from Jawaharlal Nehru Technological University-Hyderabad, India. He subsequently joined in Ewha Womans University, Korea and in 2017 joined Prof. Jong Seung Kim lab at Korea University. Yi Zang obtained her PhD from SIMM (CAS) in 2008 and is currently a professor at Lingang Laboratory. Her research mainly focuses on the biological research of AMPK, drug discovery for organ fibrosis and development of new chemical biology probe tools. Adam C. Sedgwick (Left) is a Glasstone Research Fellow at the University of Oxford and is a Junior Research Fellow at Jesus College, Oxford. His research focus is on developing new chemical tools for molecular imaging, sensing, and theranostic applications. His h-index is 29 (Google Scholar). Tony D. James (Centre) is a Professor at The University of Bath and Fellow of the Royal Society of Chemistry. His research interests include many aspects of Supramolecular chemistry, including probes for redox imbalance and theranostic systems. His h-index is 80 (Google Scholar). Luling Wu (Right) was awarded scholarships by the China Scholarship Council and University of Bath to carry out a PhD at the University of Bath. His research focuses on fluorescent probes/prodrugs and imaging. His h-index is 17. Hai-Hao Han is an Associate Professor at SIMM (CAS). He received his PhD in 2020 from ECUST under the supervision of Prof. Xiao-Peng He. His research interests include fluorescent probes for disease theranostic applications and targeted drug development. Xiao-Peng He is a professor at Feringa Nobel Prize Scientists Research Center, ECUST. He obtained his BSc (2006) and PhD (2011) from ECUST. He conducted postdoctoral research with Kaixian Chen (SIMM, CAS) from 2011 to 2013 at ECUST. His research interests are chemical probes for glycobiology and sugar-based drug discovery. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 |
| ISSN: | 0306-0012 1460-4744 1460-4744 |
| DOI: | 10.1039/d2cs00673a |