Attractive results have been achieved with small-molecule target-based drugs in the anticancer field; however, enhancing their treatment effect and solving the problem of drug resistance remain key concerns worldwide. Inspired by the specific affinity of gefitinib for tumour cells and the strong oxidation capacity of singlet oxygen, we combined a chemically generated singlet oxygen moiety with the small-molecule targeted drug gefitinib to improve its anticancer effect. We designed and synthesised a novel compound (Y5-1), in which a small-molecule targeted therapy agent (gefitinib) and a singlet oxygen (provided by an in vitro photodynamic reaction) thermally controlled releasing moiety are covalently conjugated. We demonstrated that the introduction of the singlet oxygen thermally controlled releasing moiety enhanced the anticancer activities of gefitinib. The results of this study are expected to provide a novel strategy to enhance the effect of chemotherapy drugs on drug-resistant cell lines.

中文翻译：

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用单线态氧释放部分武装后，吉非替尼在药物敏感性和耐药性癌细胞系中的功效增强。

在抗癌领域中，基于小分子靶标的药物已经获得了引人注目的结果。但是，提高其治疗效果和解决耐药性问题仍然是全世界的主要关注问题。受吉非替尼对肿瘤细胞的特异性亲和力和单线态氧强大的氧化能力的启发，我们将化学生成的单线态氧部分与小分子靶向药物吉非替尼结合起来，以提高其抗癌作用。我们设计并合成了一种新型化合物（Y5-1），其中小分子靶向治疗剂（gefitinib）和单线态氧（通过体外光动力反应提供）热控制释放部分共价结合。我们证明单线态氧热控制释放部分的引入增强了吉非替尼的抗癌活性。预期这项研究的结果将提供一种新的策略，以增强化疗药物对耐药细胞系的作用。