化学
费斯特共振能量转移
前药
荧光
光动力疗法
药物输送
纳米载体
部分
共轭体系
生物物理学
组合化学
纳米技术
聚合物
有机化学
立体化学
生物化学
生物
量子力学
物理
材料科学
作者
Wenfang Jin,Bin Fan,Xinrui Qin,Yuxia Liu,Qian Cui,Bo Tang,Tony D. James,Guang Chen
标识
DOI:10.1016/j.ccr.2022.214999
摘要
As an important anticancer drug, chlormethine has been used for more than 70 years. Owing to its good efficacy and adaptable structure, chlormethine has been integrated with trackable prodrugs, for the investigation of drug control and tumor targeting. Given the increasing importance of precision medicine, with this review we collate the structure–activity and trackable strategies used for chlormethine-based prodrugs: 1) Small molecule prodrugs: structural transformation of closed spiropyran (SP) to zwitterionic merocyanin (MC), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET) and excited-state intramolecular proton transfer (ESIPT) can enable the fluorescence monitoring or quantification of chlormethine release; 2) Polymer prodrugs: using a conjugated backbone or incorporating fluorophores into side chains, polymers can regulate the emission (π-π interactions or aggregation-induced emission (AIE) mechanisms) and control the release of chlormethine; 3) Nanosystem prodrugs: drug release visualized by the triggered rupture, deformation or degradation of the nanocarrier; 4) Chlormethine-based fluorescent probes: the chlormethine moiety can enable mitochondrial DNA or tumor cells targeting, thereby providing probes for subcellular-labelling. 5) Multifunctional fluorescence prodrugs: modification of chlormethine with fluorescent photodynamic therapeutic (PDT) or photothermal therapeutic (PTT) agents, can achieve visible multimodal therapy, involving chemotherapy CT-PDT, CT-PTT and CT-PDT-PTT. These strategies have enabled the development of fluorescent prodrugs using chlormethine, and these approaches will be covered in this review. We envision that such structure–activity relationships will be particularly important for the future development of anticancer drugs suitable for precision medicine.
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