Multifunctional Nanodiamond Conjugate With a Tumor‐Specific EGFR‐Targeting Peptide and Photoactivated CO Release for Improved Therapeutic Efficacy in Head and Neck Cancers

ABSTRACT The targeted and stimuli‐responsive delivery of drugs for the treatment of cancer using functionalized nanoparticles is a promising avenue for therapeutic applications. However, many of these conjugates are limited by either low biocompatibility, poor targeting efficiency or complex requirements for the response to stimuli. Here we report a highly efficient nanodiamond conjugate for the light induced delivery of carbon monoxide, a potent anti‐tumor agent. Nanodiamond particles are well‐known for their high biocompatibility, rich surface chemistry, and low cytotoxicity. Using co‐functionalization with an EGFR‐targeting peptide and a manganese carbonyl complex as PhotoCORM, the efficient delivery of CO to cancer cells is demonstrated with spatiotemporal resolution both in vitro and in vivo using blue‐light photoactivation. In vitro experiments using head and neck cancer models show significant cancer‐specific cytotoxicity only upon blue‐light exposure, whereas limited toxicity was observed toward non‐cancerous and pre‐malignant cells. Further in vivo experiments demonstrate the significant suppression of tumor growth and lymph node metastasis in a head and neck cancer xenograft mouse model while maintaining excellent biocompatibility. This paves the way for the application of multifunctional, nanodiamond‐based delivery tools in the stimuli responsive treatment of tumors.