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

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.