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Tetrazine-Mediated Bioorthogonal System for Prodrug Activation, Photothermal Therapy, and Optoacoustic Imaging
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-10-31 , DOI: 10.1021/acsami.9b13374
Xin xie 1 , Bowen Li 1 , Jie Wang 1 , Chenyue Zhan 1 , Yong Huang 1 , Fang Zeng 1 , Shuizhu Wu 1
Affiliation  

Bioorthogonal “bond cleavage” reactions hold great promise in a variety of biological applications such as controlled activation of the drug and probe, while the application of these biocompatible reactions in living animals is still in its infancy and has yet to be further explored. Herein we demonstrate a nanosized and two-component bioorthogonal system for tumor inhibition through the combined action of chemo- and photothermal therapy. The trigger of the system was fabricated by immobilizing PEGylated tetrazine on the gold nanorods, and the bioorthogonal prodrug was synthesized by caging the drug camptothecin with vinyl ether, followed by encapsulating it with phospholipid liposomes. The tetrazine-based trigger effectively mediates the bioorthogonal reaction and triggers the release of camptothecin for chemotherapy, and the gold nanorods exhibit high photothermal capability for photothermal therapy and for three-dimensional optoacoustic imaging. Upon injection into tumor-bearing mice, the two components accumulate in the tumor region and carry out a bioorthogonal reaction therein, hence releasing the parent drug. The combined actions of chemo- and photothermal therapy greatly inhibited tumor growth in mice. This strategy may afford a promising approach for achieving controlled release of an active drug in vivo through an alternative external stimulus—a bioorthogonal reaction.

中文翻译:

Tetrazine介导的生物正交系统,用于前药激活,光热疗法和光声成像

正交的“键裂解”反应在多种生物学应用中具有广阔的前景,例如药物和探针的受控活化,而这些生物相容性反应在活体动物中的应用仍处于起步阶段,尚待进一步探索。在这里,我们展示了通过化学和光热疗法的联合作用来抑制肿瘤的纳米级和两组分生物正交系统。通过将PEG化的四嗪固定在金纳米棒上来制造该系统的触发物,并通过用乙烯基醚封闭喜树碱药物,然后用磷脂脂质体封装来合成生物正交前药。基于四嗪的触发器可有效介导生物正交反应并触发喜树碱的释放,以进行化学治疗,金纳米棒对光热疗法和三维光声成像具有很高的光热能力。注射到荷瘤小鼠中后,这两种成分在肿瘤区域积聚并在其中进行生物正交反应,从而释放出母体药物。化学和光热疗法的联合作用极大地抑制了小鼠的肿瘤生长。该策略可能为通过替代性外部刺激(生物正交反应)实现活性药物在体内的受控释放提供一种有前途的方法。化学和光热疗法的联合作用极大地抑制了小鼠的肿瘤生长。该策略可能为通过替代性外部刺激(生物正交反应)实现活性药物在体内的受控释放提供一种有前途的方法。化学和光热疗法的联合作用极大地抑制了小鼠的肿瘤生长。该策略可能为通过替代性外部刺激(生物正交反应)实现活性药物在体内的受控释放提供一种有前途的方法。
更新日期:2019-11-01
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