Platinum-drug-based chemotherapy in clinics has achieved great success in clinical malignancy therapy. However, unpredictable off-target toxicity and the resulting severe side effects in the treatment are still unsolved problems. Although metabolic glycan labeling-mediated tumor-targeted therapy has been widely reported, less selective metabolic labeling in vivo limited its wide application. Herein, a novel probe of B–Ac₃ManNAz that is regulated by reactive oxygen species in tumor cells is introduced to enhance the recognition and cytotoxicity of DBCO-modified oxaliplatin(IV) via bioorthogonal chemistry. B–Ac₃ManNAz was synthesized from Ac₄ManNAz by incorporation with 4-(hydroxymethyl) benzeneboronic acid pinacol ester (HBAPE) at the anomeric position, which is confirmed to be regulated by ROS and could robustly label glycans on the cell surface. Moreover, N₃-treated tumor cells could enhance the tumor accumulation of DBCO-modified oxaliplatin(IV) via click chemistry meanwhile reduce the off-target distribution in normal tissue. Our strategy provides an effective metabolic precursor for tumor-specific labeling and targeted cancer therapies.

中文翻译：

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基于 ROS 调节的癌症选择性聚糖标记的肿瘤靶向奥沙利铂 (IV) 前药递送


临床上以铂类药物为基础的化疗在临床恶性肿瘤治疗中取得了巨大成功。然而，不可预测的脱靶毒性以及治疗中由此产生的严重副作用仍然是尚未解决的问题。尽管代谢聚糖标记介导的肿瘤靶向治疗已被广泛报道，但体内代谢标记选择性较低限制了其广泛应用。在此，引入了一种受肿瘤细胞中活性氧调节的 B–Ac ₃ ManNAz 新型探针，通过生物正交化学增强了 DBCO 修饰的奥沙利铂 (IV) 的识别和细胞毒性。 B–Ac ₃ ManNAz 由 Ac ₄ ManNAz 通过在异头位置掺入 4-(羟甲基) 苯硼酸频哪醇酯 (HBAPE) 合成，已证实其受ROS 可以在细胞表面强有力地标记聚糖。此外，N ₃ 处理的肿瘤细胞可以通过点击化学增强 DBCO 修饰的奥沙利铂（IV）的肿瘤积累，同时减少正常组织中的脱靶分布。我们的策略为肿瘤特异性标记和靶向癌症治疗提供了有效的代谢前体。