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

Sep 22, 2026

Targeted, stimuli-responsive drug delivery using functionalized nanoparticles offers strong therapeutic potential but is often limited by inadequate biocompatibility, insufficient targeting, or burdensome stimulus-response requirements. This study presents a multifunctional nanodiamond conjugate enabling light-induced carbon monoxide delivery as an anti-tumor strategy. Co-functionalization with an EGFR-targeting peptide and a manganese carbonyl PhotoCORM supports efficient, blue-light-triggered CO release with spatiotemporal control. Head and neck cancer models show cancer-selective cytotoxicity upon blue-light exposure with minimal effects on noncancerous and pre-malignant cells, while in vivo xenograft results demonstrate suppressed tumor growth and lymph node metastasis while retaining excellent biocompatibility.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Nanodiamond properties and biomedical applications

Nanodiamond drug delivery and surface functionalization

Targeting and stimuli-responsive improvements

Small [www.small-journal.com](www.small-journal.com) RESEARCH ARTICLE Multifunctional Nanodiamond Conjugate With a Tumor-Specific EGFR-Targeting Peptide and Photoactivated CO Release for Improved Therapeutic Efficacy in Head and Neck Cancers Harsh Nitin Dongre1, 2 Elisabeth Mayerhoefer3 Julia Puck4 Himalaya Parajuli1, 2 Lorena Larios Salazar1, 2 Paul Johan Høl5, 6 Ridhima Das1, 2 Patrick Roth7 Christian Arvei Moen8 Ulrich Schatzschneider7 Line Bjørge2, 9 Daniela Elena Costea1, 2, 10 Anke Krueger3, 11 1The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway 2 Centre for Cancer Biomarkers, Faculty of Medicine, University of Bergen, Bergen, Norway 3 Institute of Organic Chemistry, University of Stuttgart, Stuttgart, Germany 4 Institute of Organic Chemistry, Julius-Maximilians-Universität Würzburg, Würzburg, Germany 5 Department of Clinical Medicine, University of Bergen, Bergen, Norway 6 Biomatlab, Department of Orthopaedic Surgery, Haukeland University Hospital, Bergen, Norway 7 Institute of Inorganic Chemistry, Julius-MaximiliansUniversität Würzburg, Würzburg, Germany 8 Department of Urology, Haukeland University Hospital, Bergen, Norway 9 Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway 10 Department of Pathology, Haukeland University Hospital, Bergen, Norway 11 Center for Integrated Quantum Science and Technology, University of Stuttgart, Stuttgart, Germany Correspondence: Daniela Elena Costea ([daniela.costea@uib.no](daniela.costea@uib.no)) Anke Krueger (anke.krueger@oc.uni-stuttgart.de) Received: 13 January 2026 Revised: 22 May 2026 Accepted: 12 June 2026 Keywords: cancer treatment | diamond nanoparticles | nanocarbon | photoCORM | stimuli-responsive targeted drug delivery | surface chemistry 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 noncancerous 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. Harsh Nitin Dongre and Elisabeth Mayerhoefer contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2026 The Author(s). Small published by Wiley-VCH GmbH Small, 2026; 22:e74355 [https://doi.org/10.1002/smll.74355](https://doi.org/10.1002/smll.74355) 1 of 16 1 Introduction Nanodiamond (ND) particles have been identified as one of the most promising materials for biomedical applications due to their high biocompatibility, low toxicity, and facile chemical surface modification [1–3] . Applications of ND include sensing of metabol

FAQs

What problem does the multifunctional nanodiamond conjugate aim to solve in cancer therapy?

It addresses limitations of nanoparticle conjugates such as low biocompatibility, poor targeting efficiency, and complex stimulus-response requirements by enabling light-induced, targeted delivery of carbon monoxide.

How is carbon monoxide delivered to cancer cells in this approach?

Nanodiamond particles are co-functionalized with an EGFR-targeting peptide and a manganese carbonyl complex (PhotoCORM), and carbon monoxide is released upon blue-light photoactivation with spatiotemporal control.

What results were observed in vitro and in vivo for head and neck cancer models?

In vitro, significant cancer-specific cytotoxicity occurs only with blue-light exposure and limited toxicity is seen toward noncancerous and pre-malignant cells. In vivo, tumor growth and lymph node metastasis are suppressed in a head and neck cancer xenograft mouse model while maintaining strong biocompatibility.

Sep 22, 2026

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