A nanoplatform based on allylthiopurine bio-MOF and glycosylated AIE PARP inhibitor for cancer synthetic lethal therapy,Chemical Communications

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A nanoplatform based on allylthiopurine bio-MOF and glycosylated AIE PARP inhibitor for cancer synthetic lethal therapy
Chemical Communications ( IF 4.3 ) Pub Date : 2024-07-26 , DOI: 10.1039/d4cc02944e
Bingling Gao ₁ , Ke Yang ₁ , Manman Yang ₁ , Wendong Li ₁ , Tingli Jiang ₁ , Rong Gao ₁ , Yuxin Pei ₁ , Zhichao Pei ₁ , Yinghua Lv ₁

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A biological nanoplatform (Gal-ANI@ZnAP NPs) was constructed based on a prodrug-skeletal metal–organic framework (MOF) using purine nucleobase analogue prodrug 6-allylthiopurine as a bioactive ligand, and functionalized with AIE fluorescent PARP inhibitor glycoconjugate for visualization therapy and synthetic lethal cancer therapy. This nanoplatform could actively target cancer cells, selectively release drugs in response to esterase/pH, and visualize drug uptake. In vitro studies revealed that Gal-ANI@ZnAP NPs increased the synthetic lethality in cancer cells by inducing DNA repair failure with the simultaneous targeting of PARP and nucleotide metabolism, thereby exhibiting a significant cancer-killing effect. The study presents a novel strategy to construct an AIE nanoplatform using pharmaceutical molecules for drug uptake visualization and boosting synthetic lethality in cancer.

中文翻译：

基于烯丙基硫嘌呤生物MOF和糖基化AIE PARP抑制剂的用于癌症合成致死治疗的纳米平台

使用嘌呤核碱基类似物前药 6-烯丙基硫嘌呤作为生物活性配体，基于前药-骨架金属有机框架 (MOF) 构建了生物纳米平台 (Gal-ANI@ZnAP NPs)，并用 AIE 荧光 PARP 抑制剂糖缀合物进行功能化，用于可视化治疗和合成致死性癌症治疗。该纳米平台可以主动靶向癌细胞，根据酯酶/pH 选择性释放药物，并可视化药物摄取。体外研究表明，Gal-ANI@ZnAP NPs 通过诱导 DNA 修复失败，同时靶向 PARP 和核苷酸代谢，增加了癌细胞的合成致死率，从而表现出显着的抗癌作用。该研究提出了一种利用药物分子构建 AIE 纳米平台的新策略，用于药物摄取可视化并提高癌症的合成致死率。

更新日期：2024-07-26

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