Tetrazine Carbon Nanotubes for Pretargeted In Vivo "Click-to-Release" Bioorthogonal Tumour Imaging.,Angewandte Chemie International Edition

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Tetrazine Carbon Nanotubes for Pretargeted In Vivo "Click-to-Release" Bioorthogonal Tumour Imaging.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-06-18 , DOI: 10.1002/anie.202008012
He Li ₁ , João Conde ₂ , Ana Guerreiro ₂ , Gonçalo J L Bernardes _{1,

2}

Affiliation

The bioorthogonal inverse‐electron‐demand Diels–Alder (IEDDA) cleavage reaction between tetrazine and trans‐cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single‐walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO‐caged molecule was used to deliver active effector molecules. To optimize a turn‐on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near‐infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real‐time, non‐invasive tumour visualization with a high target‐to‐background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine‐functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off‐site activation of fluorophore/drug.

中文翻译：

用于预先靶向体内“点击释放”生物正交肿瘤成像的四嗪碳纳米管。

四嗪与反式之间的生物正交逆电子需求Diels-Alder（IEDDA）裂解反应环辛烯（TCO）是控制生物活性剂和成像探针释放的有效方法。在本研究中，使用带有四嗪（TZ @ SWCNT）的单壁碳纳米管（SWCNT）和TCO笼蔽分子的预靶向激活策略来递送活性效应分子。为了通过使用体内荧光成像来优化开启信号，我们开发了一种新型的荧光近红外探针，该探针可以通过生物正交化学激活，并通过用TCO笼罩半胱氨酸（tHCA）在小鼠中成像肿瘤。通过我们的预靶向策略，我们已经显示了活细胞中的选择性阿霉素前药激活和瞬时荧光成像。通过将tHCA探针和预定位的生物正交方法相结合，实时，在异种移植小鼠肿瘤模型中实现了具有高目标背景比的无创肿瘤可视化。四嗪功能化的SWCNT具有增强的稳定性，动力学和生物相容性以及优异的药代动力学的综合优势，可以应用针对性的生物正交降解方法，而场外荧光团/药物的激活最少。

更新日期：2020-06-18

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