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

ABSTRACT

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 (d OR6 ‐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 d OR6 ‐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.