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A Bioorthogonal Decaging Chemistry of N-Oxide and Silylborane for Prodrug Activation both In Vitro and In Vivo
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-11-07 , DOI: 10.1021/jacs.3c08012 Zhicheng Yan 1 , Yiyao Pan 1 , Guofeng Jiao 1 , Mengyu Xu 2 , Dongguang Fan 1 , Ziwei Hu 1 , Jiarui Wu 1 , Tao Chen 1 , Miao Liu 1 , Xiaoguang Bao 2 , Hengte Ke 1 , Xingyue Ji 1
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-11-07 , DOI: 10.1021/jacs.3c08012 Zhicheng Yan 1 , Yiyao Pan 1 , Guofeng Jiao 1 , Mengyu Xu 2 , Dongguang Fan 1 , Ziwei Hu 1 , Jiarui Wu 1 , Tao Chen 1 , Miao Liu 1 , Xiaoguang Bao 2 , Hengte Ke 1 , Xingyue Ji 1
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Bioorthogonal decaging chemistry with both fast kinetics and high efficiency is highly demanded for in vivo applications but remains very sporadic. Herein, we describe a new bioorthogonal decaging chemistry between N-oxide and silylborane. A simple replacement of “C” in boronic acid with “Si” was able to substantially accelerate the N-oxide decaging kinetics by 106 fold (k2: up to 103 M–1 s–1). Moreover, a new N-oxide-masked self-immolative spacer was developed for the traceless release of various payloads upon clicking with silylborane with fast kinetics and high efficiency (>90%). Impressively, one such N-oxide-based self-assembled bioorthogonal nano-prodrug in combination with silylborane led to significantly enhanced tumor suppression effects as compared to the parent drug in a 4T1 mouse breast tumor model. In aggregate, this new bioorthogonal click-and-release chemistry is featured with fast kinetics and high efficiency and is perceived to find widespread applications in chemical biology and drug delivery.
中文翻译：
用于体外和体内前药激活的 N-氧化物和甲硅烷基硼烷的生物正交解腐化学
体内应用非常需要具有快速动力学和高效率的生物正交解腐化学，但仍然非常零星。在此，我们描述了N-氧化物和甲硅烷基硼烷之间的一种新的生物正交解腐化学。用“Si”简单替换硼酸中的“C”能够将N-氧化物脱腐动力学显着加速10 6倍（ k 2 ：高达10 3 M –1 s –1 ）。此外，还开发了一种新的N-氧化物掩蔽自焚间隔物，用于在与甲硅烷基硼烷点击时无痕释放各种有效负载，具有快速动力学和高效率（> 90％）。令人印象深刻的是，在4T1小鼠乳腺肿瘤模型中，与母体药物相比，这种基于N-氧化物的自组装生物正交纳米前药与甲硅烷基硼烷的组合显着增强了肿瘤抑制效果。总的来说，这种新的生物正交点击释放化学具有快速动力学和高效率的特点，被认为在化学生物学和药物输送领域有广泛的应用。
更新日期：2023-11-07
中文翻译：
用于体外和体内前药激活的 N-氧化物和甲硅烷基硼烷的生物正交解腐化学
体内应用非常需要具有快速动力学和高效率的生物正交解腐化学，但仍然非常零星。在此，我们描述了N-氧化物和甲硅烷基硼烷之间的一种新的生物正交解腐化学。用“Si”简单替换硼酸中的“C”能够将N-氧化物脱腐动力学显着加速10 6倍（ k 2 ：高达10 3 M –1 s –1 ）。此外，还开发了一种新的N-氧化物掩蔽自焚间隔物，用于在与甲硅烷基硼烷点击时无痕释放各种有效负载，具有快速动力学和高效率（> 90％）。令人印象深刻的是，在4T1小鼠乳腺肿瘤模型中，与母体药物相比，这种基于N-氧化物的自组装生物正交纳米前药与甲硅烷基硼烷的组合显着增强了肿瘤抑制效果。总的来说，这种新的生物正交点击释放化学具有快速动力学和高效率的特点，被认为在化学生物学和药物输送领域有广泛的应用。
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