Han Hai-Hao, Wang Han-Min, Jangili Paramesh, Li Mingle, Wu Luling, Zang Yi, Sedgwick Adam C, Li Jia, He Xiao-Peng, James Tony D, Kim Jong Seung
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Rd., Shanghai 200237, P. R. China.
State Key Laboratory of Drug Research, Molecular Imaging Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Chem Soc Rev. 2023 Feb 6;52(3):879-920. doi: 10.1039/d2cs00673a.
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.
癌症仍然是最严重的健康问题之一，全球每年约有1900万人被诊断患有癌症。化疗是治疗癌症患者的常用方法。然而，目前的治疗方案对癌细胞缺乏适当的选择性，容易产生耐药机制，并且受到剂量限制性毒性的困扰。因此，研究人员致力于开发基于前药的策略，这些策略有可能克服这些局限性。本教程综述重点介绍了最近开发的用于癌症治疗的前药策略。还讨论了提供综合诊断（荧光、光声和磁共振成像）响应的前药实例，即所谓的诊疗一体化。由于光（和X射线）的非侵入性，我们讨论了外部激发前药策略以及可激活光敏剂的实例，这些可激活光敏剂提高了光动力疗法/光热疗法的精确性。可激活光敏剂/光热剂可被视为类似于前药，其在疾病相关生物标志物存在的情况下在特定波长下的光治疗特性被激活。我们讨论了每种设计策略，并说明了靶向肿瘤微环境特有的生物标志物以及已知在癌细胞中过度表达的生物标志物的重要性。此外，我们讨论了每种方法的优点，并强调了它们固有的局限性。我们希望通过这样做，读者将了解该领域当前的挑战和可用机会，并激励后代在这个关键的癌症研究领域继续探索。
