The design of small-molecule prodrugs and activatable phototherapeutics for cancer therapy

被引:145
作者
Han, Hai-Hao [1 ,2 ,4 ,6 ,9 ]
Wang, Han-Min [4 ,6 ]
Jangili, Paramesh [5 ]
Li, Mingle [5 ]
Wu, Luling [3 ]
Zang, Yi [4 ]
Sedgwick, Adam C. [7 ]
Li, Jia [4 ,6 ,9 ]
He, Xiao-Peng [1 ,2 ,10 ,11 ]
James, Tony D. [3 ,8 ]
Kim, Jong Seung [5 ]
机构
[1] East China Univ Sci & Technol, Sch Chem & Mol Engn, Key Lab Adv Mat, 130 Meilong Rd, Shanghai 200237, Peoples R China
[2] East China Univ Sci & Technol, Sch Chem & Mol Engn, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Ctr Materiobiol & Dynam Chem,Joint Int R, 130 Meilong Rd, Shanghai 200237, Peoples R China
[3] Univ Bath, Dept Chem, Bath BA2 7AY, England
[4] Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
[5] Korea Univ, Dept Chem, Seoul 02841, South Korea
[6] Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
[7] Univ Oxford, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England
[8] Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China
[9] Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
[10] Eastern Hepatobiliary Surg Hosp, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China
[11] Natl Ctr Liver Canc, Shanghai 200438, Peoples R China
基金
新加坡国家研究基金会; 中国国家自然科学基金; 中国博士后科学基金; 美国国家科学基金会;
关键词
GAMMA-GLUTAMYL-TRANSPEPTIDASE; RESPONSIVE DRUG-DELIVERY; HYDROGEN-PEROXIDE; TUMOR MICROENVIRONMENT; PHOTODYNAMIC THERAPY; OXIDATIVE STRESS; RATIONAL DESIGN; NANOPARTICLES; DOXORUBICIN; SYSTEMS;
D O I
10.1039/d2cs00673a
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:879 / 920
页数:42
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