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Biofunctionalization of Magnetic Nanomaterials
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Targeting Nanomaterials to Head and Neck Cancer Cells Using a Fragment of the Shiga Toxin as a Potent Natural Ligand
Elena Navarro-Palomares1, Lorena García-Hevia1, Esperanza Padín-González1
1The Nanomedicine Group, Institute Vadecilla-IDIVAL, Molecular Biology and Anatomy & Cell Biology Departments, Faculty of Medicine, University of Cantabria, Avda. Cardenal Herrera Oria, 39011 Santander, Spain.
Abstract:
Head and Neck Cancer (HNC) is the seventh most common cancer worldwide with a 5-year survival from diagnosis of 50%. Currently, HNC is diagnosed by a physical examination followed by an histological biopsy, with surgery being the primary treatment. Here, we propose the use of targeted nanotechnology in support of existing diagnostic and therapeutic tools to prevent recurrences of tumors with poorly defined or surgically inaccessible margins. We have designed an innocuous ligand-protein, based on the receptor-binding domain of the Shiga toxin (ShTxB), that specifically drives nanoparticles to HNC cells bearing the globotriaosylceramide receptor on their surfaces. Microscopy images show how, upon binding to the receptor, the ShTxB-coated nanoparticles cause the clustering of the globotriaosylceramide receptors, the protrusion of filopodia, and rippling of the membrane, ultimately allowing the penetration of the ShTxB nanoparticles directly into the cell cytoplasm, thus triggering a biomimetic cellular response indistinguishable from that triggered by the full-length Shiga toxin. This functionalization strategy is a clear example of how some toxin fragments can be used as natural biosensors for the detection of some localized cancers and to target nanomedicines to HNC lesions.
Insights
Researchers developed Shiga toxin-based nanoparticles to target head and neck cancer (HNC) cells. This nanotechnology offers a novel approach for detecting and treating HNC, potentially improving patient outcomes.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Head and Neck Cancer (HNC) is a significant global health concern with a 5-year survival rate of 50%.
- Current HNC diagnosis relies on physical examination and biopsy, with surgery as the primary treatment.
- Tumor recurrences due to poorly defined or inaccessible margins remain a clinical challenge.
Purpose of the Study:
- To investigate the use of targeted nanotechnology for detecting and treating HNC.
- To develop a novel nanomedicine delivery system for HNC lesions.
- To explore the potential of toxin fragments as biosensors and therapeutic agents for HNC.
Main Methods:
- Designed innocuous ligand-protein nanoparticles using the Shiga toxin fragment (ShTxB).
- Functionalized nanoparticles to target HNC cells expressing the globotriaosylceramide receptor.
- Utilized microscopy to observe nanoparticle-cell interactions and cellular responses.
Main Results:
- ShTxB-coated nanoparticles specifically bound to HNC cells expressing the globotriaosylceramide receptor.
- Nanoparticle binding induced receptor clustering, membrane rippling, and filopodia protrusion.
- Nanoparticles successfully penetrated the cell cytoplasm, triggering a biomimetic cellular response.
Conclusions:
- The Shiga toxin fragment (ShTxB) can be effectively utilized as a targeting ligand for HNC.
- This nanotechnology-based approach shows promise for early cancer detection and targeted nanomedicine delivery.
- Toxin fragments serve as valuable tools for developing novel diagnostic and therapeutic strategies against HNC.
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