Targeted NIR‐II Photothermal Therapy Enabled by Bioorthogonal Click Reaction With Olympicenyl Radical Nanoparticles

This study presents an application of delocalized hydrocarbon neutral monoradical, an olympicenyl radical (OR6), as a high-performance organic photothermal agent (PTA) for targeted photothermal therapy (PTT). By encapsulating OR6 into functionalized nanoparticles (dOR6-NPs), a remarkable near-infrared-II (NIR-II) absorption at 1056 nm and photothermal conversion efficiency (PCE) of 84.66% are achieved. To overcome the limitations of passive tumor targeting, a bioorthogonal "tag-and-target" strategy is developed using metabolic glycan labeling and copper-free click reaction. This approach significantly enhanced photothermal therapeutic efficacy both in vitro and in vivo. The dOR6-NPs induce significant cytotoxicity of cancer cells under 1064 nm laser irradiation, leading to nearly complete tumor suppression in a xenograft model while maintaining excellent biocompatibility and systemic safety. This work not only highlights olympicenyl radicals as a new class of PTAs but also establishes a robust click-reaction-based platform for precision cancer therapy.