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.