A Motor-Based Carbonaceous Nanocalabash Catalyst for Deep-Layered Bioorthogonal Chemistry

Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has been widely regarded as a promising avenue in bioorthogonal chemistry. The emerging heterogeneous copper catalysts have been developed with a series of exciting applications such as in situ activation of prodrugs because of their excellent stability and biocompatibility. However, due largely to the complex biophysical barriers in living organisms, most synthetic bioorthogonal drugs cannot penetrate deep pathological tissues. Especially in biofilm-associated infections, the biofilms severely block the penetration of traditional antimicrobial agents and increase the antibiotic resistance, which makes it extremely difficult to eliminate the biofilms. Inspired by self-propelled biological motors, such as enzymes, herein, we develop a NIR light-controllable carbonaceous nanocalabash (CNC) motor catalyst with good biocompatibility for active targeted synthesis of drugs inside the biofilms as a robust general-purpose bioorthogonal platform. Under the NIR laser, the CNC motor catalysts display a rapid autonomous motion and generate active molecules in the deep biofilm layers, removing the biofilms and eradicating the shielded bacteria. Our work will shed light on developing a robust bioorthogonal platform for active targeted synthesis of drugs in deep-layered living systems.