Nanocopper-Doped Cross-Linked Lipoic Acid Nanoparticles for Morphology-Dependent Intracellular Catalysis

The metal catalysts encapsulated in nanomaterials have recently been applied successfully in bioorthogonal chemistry for intracellular generation of bioactive compounds. However, the nanomaterial-involved intracellular catalysis is intrinsically different from that in solution or in extracellular fluid. Except for the reactivity of metal catalyst itself, the supporting material’s morphology and biocompatibility are essential factors for building optimal nanocatalysts. Herein, we present a new nanocopper-doped cross-linked lipoic acid nanoparticle (Cu@cLANP) that meets the stringent requirements for the intracellular nanocatalyst. It comes from endogenous lipoic acid and can easily achieve the morphology change by different reduction methods. The optimal rugbylike Cu@cLANPs I did show much better catalytic efficiency for intracellular azide–alkyne cycloaddition than that of the other two spherical nanocatalysts Cu@cLANPs II and III, hinting at the importance of nanoparticle morphology for the intracellular bioorthogonal transformation.