[60]Fullerene–Cluster Hybrids as Boron‐Dense Delivery Nanoplatforms

Boron Neutron Capture Therapy (BNCT) relies on the accumulation of boron‐10 within tumor cells to induce highly localized cytotoxicity upon neutron irradiation. The development of boron delivery systems with high boron content, biocompatibility, and efficient cellular uptake remains a critical challenge. Herein, we report the design and synthesis of unprecedented fullerene–boron cluster hybrids that integrate the multivalent scaffold of [60]fullerene with anionic boron clusters. Two [60]fullerene hexakis‐adducts bearing twelve peripheral cobaltabisdicarbollide (COSAN) or closo ‐dodecaborate boron clusters have been prepared through a Cu(I)‐catalyzed azide–alkyne cycloaddition strategy. The resulting nanostructures incorporate up to 216 boron atoms while preserving the structural integrity of both the fullerene core and the anionic boron clusters. Comprehensive spectroscopic and electrochemical characterization confirms the successful formation of the hybrids. To enable biological evaluation, the compounds are formulated into liposomes, showing excellent cytocompatibility and efficient cellular internalization in mouse embryonic fibroblasts and Cal33 human head and neck cancer cells. Confocal microscopy reveals predominant endolysosomal localization without significant cytotoxicity at therapeutically relevant boron concentrations. These results establish fullerene–boron cluster conjugates as a new class of boron‐rich nanomaterials and highlight their potential as boron delivery agents for future BNCT studies.