Nanodiamond conjugate with EGFR-targeting peptide and photoactivated CO release suppresses head and neck tumor growth.

Effective treatment for head and neck cancers (HNC) remains challenging due to issues like drug resistance, systemic toxicity, and poor targeting efficiency of conventional therapies. Nanomedicine offers a promising avenue, but many nanoparticle conjugates face limitations in biocompatibility, precise targeting, or complex stimuli requirements. Targeting the Epidermal Growth Factor Receptor (EGFR), which is often overexpressed in HNC, provides a specific pathway for drug delivery. This study addresses the need for a highly efficient, biocompatible, and stimuli-responsive delivery system for potent anti-tumor agents like carbon monoxide (CO) to improve therapeutic outcomes in HNC.

Researchers engineered a multifunctional nanodiamond conjugate by co-functionalizing nanodiamond particles with an EGFR-targeting peptide and a manganese carbonyl complex (PhotoCORM) for light-induced CO release. The efficacy of this conjugate was evaluated in vitro using head and neck cancer cell models, alongside non-cancerous and pre-malignant cells, to assess cancer-specific cytotoxicity upon blue-light photoactivation. Further in vivo experiments were conducted in a head and neck cancer xenograft mouse model. The primary endpoints included assessing tumor growth suppression, lymph node metastasis, and overall biocompatibility of the nanodiamond conjugate under blue-light exposure.

The nanodiamond conjugate demonstrated efficient delivery of carbon monoxide (CO) to cancer cells with spatiotemporal resolution upon blue-light photoactivation, both in vitro and in vivo. In vitro experiments using head and neck cancer models showed significant cancer-specific cytotoxicity, but only when exposed to blue light. Importantly, limited toxicity was observed toward non-cancerous and pre-malignant cells, highlighting the conjugate's selective action. The most critical finding from the study was observed in vivo:

The multifunctional nanodiamond conjugate led to significant suppression of tumor growth and lymph node metastasis in a head and neck cancer xenograft mouse model. This therapeutic effect was achieved while maintaining excellent biocompatibility, suggesting a favorable safety profile for the delivery system. The precise mechanism involves EGFR-mediated targeting and subsequent photoactivated CO release, which acts as a potent anti-tumor agent, disrupting cancer cell proliferation and spread.