Wang Hua, Gauthier Marianne, Kelly Jamie R, Miller Rita J, Xu Ming, O'Brien William D, Cheng Jianjun
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, USA.
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Angew Chem Int Ed Engl. 2016 Apr 25;55(18):5452-6. doi: 10.1002/anie.201509601. Epub 2016 Mar 24.
Metabolic sugar labeling followed by the use of reagent-free click chemistry is an established technique for in vitro cell targeting. However, selective metabolic labeling of the target tissues in vivo remains a challenge to overcome, which has prohibited the use of this technique for targeted in vivo applications. Herein, we report the use of targeted ultrasound pulses to induce the release of tetraacetyl N-azidoacetylmannosamine (Ac4 ManAz) from microbubbles (MBs) and its metabolic expression in the cancer area. Ac4 ManAz-loaded MBs showed great stability under physiological conditions, but rapidly collapsed in the presence of tumor-localized ultrasound pulses. The released Ac4 ManAz from MBs was able to label 4T1 tumor cells with azido groups and significantly improved the tumor accumulation of dibenzocyclooctyne (DBCO)-Cy5 by subsequent click chemistry. We demonstrated for the first time that Ac4 ManAz-loaded MBs coupled with the use of targeted ultrasound could be a simple but powerful tool for in vivo cancer-selective labeling and targeted cancer therapies.
代谢糖标记结合无试剂点击化学是一种成熟的体外细胞靶向技术。然而，在体内对靶组织进行选择性代谢标记仍然是一个有待克服的挑战，这限制了该技术在体内靶向应用中的使用。在此，我们报告了使用靶向超声脉冲诱导微泡（MBs）释放四乙酰叠氮乙酰甘露糖胺（Ac4 ManAz）及其在癌区的代谢表达。负载Ac4 ManAz的微泡在生理条件下表现出很高的稳定性，但在肿瘤局部超声脉冲存在下会迅速塌陷。从微泡中释放的Ac4 ManAz能够用叠氮基团标记4T1肿瘤细胞，并通过后续的点击化学显著提高二苯并环辛炔（DBCO）-Cy5在肿瘤中的积累。我们首次证明，负载Ac4 ManAz的微泡与靶向超声的结合可能是一种简单而强大的体内癌症选择性标记和靶向癌症治疗工具。
