Abstract

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.

Original languageEnglish
Pages (from-to)879-920
Number of pages42
JournalChemical Society Reviews
Volume52
Issue number3
Early online date13 Jan 2023
DOIs
Publication statusPublished - 13 Jan 2023

Bibliographical note

Funding Information:
X.-P. H. thanks the National Natural Science Foundation of China (No. 21788102, 91853201, 82130099 and 9185920077), the Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX03), the National Science Foundation of Shanghai (No. 21XD1404600, 21JC1406600, and 22140901000), the International Cooperation Program of Shanghai Science and Technology Committee (No. 17520750100), the Fundamental Research Funds for the Central Universities (222201717003) and the Programme of Introducing Talents of Discipline to Universities (B16017) for financial support. J. L. and Y. Z. thank the National Natural Science Foundation of China (No. 82130099, 82151219, 31871414 and 81971265) and the Shanghai Municipal Science and Technology Major Project (No. 22ZR1415200). H.-H. H. thanks the National Natural Science Foundation of China (No. 22107029) and Project funded by the China Postdoctoral Science Foundation (No. 2020M681196). T. D. J. wishes to thank the Royal Society for a Wolfson Research Merit Award and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University for support (2020ZD01). L. W. wishes to thank the China Scholarship Council and the University of Bath for supporting his PhD in the UK. J. S. K. thank the financial support received from the National Research Foundation of Korea (CRI project no. 2018R1A3B1052702, 2019M3E5D1A01068998). M. L. wishes to thank the support of the Brain Pool Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (Grant No. 2020H1D3A1A02080172, M. L.). A. C. S. would like to thank the Glasstone Research fellowship (University of Oxford) and Jesus College, Oxford for support.

ASJC Scopus subject areas

  • Chemistry(all)

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