Sharma Anjali, Mejía Diana, Regnaud Aurélie, Uhlig Nick, Li Chao-Jun, Maysinger Dusica, Kakkar Ashok
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, Quebec H3G 1Y6, Canada.
ACS Macro Lett. 2014 Oct 21;3(10):1079-1083. doi: 10.1021/mz5006298. Epub 2014 Oct 6.
We report a versatile approach in which two highly efficient chemical reactions, multicomponent A coupling and alkyne-azide click chemistry, are combined to construct dendrimer-based tools for applications in biology. Using a convergent approach, dendrons with desired architecture and an alkyne at the focal point are first assembled and then stitched together via multicomponent A coupling reaction. The desired functional groups, including a stealth agent, imaging dye, and drug molecules, could be easily covalently linked to the surfaces of these hyperbranched macromolecules using alkyne-azide click chemistry. These A-click dendrimers are noncytotoxic at concentrations as high as 1 μM and in fact reduce the toxicity of the drug. The dye-coated dendrimers specifically target and localize in lipid droplets. This unison methodology represents an attractive chemical strategy in exploiting the untapped potential of A coupling and facilitating the development of nanodevices for imaging and drug delivery.
我们报道了一种通用方法，该方法将两种高效化学反应——多组分A偶联反应和炔烃-叠氮化物点击化学相结合，构建基于树枝状大分子的工具用于生物学应用。采用汇聚法，首先组装具有所需结构且在焦点处带有炔烃的树枝状分子，然后通过多组分A偶联反应将它们拼接在一起。使用炔烃-叠氮化物点击化学，可将包括隐身剂、成像染料和药物分子在内的所需官能团轻松共价连接到这些超支化大分子的表面。这些A-点击树枝状大分子在浓度高达1 μM时无细胞毒性，实际上还降低了药物的毒性。染料包被的树枝状大分子特异性靶向并定位于脂滴中。这种统一的方法代表了一种有吸引力的化学策略，可用于挖掘A偶联尚未开发的潜力，并促进用于成像和药物递送的纳米器件的开发。
