Surface Chemistry and Specific Surface Area Rule the Efficiency of Gold Nanoparticle Sensitizers in Proton Therapy

Author:

Johny Jacob1,van Halteren Charlotte E. R.1,Cakir Fatih‐Can1,Zwiehoff Sandra1,Behrends Carina234,Bäumer Christian2345,Timmermann Beate2356,Rauschenbach Laurèl3578,Tippelt Stephan9,Scheffler Björn358,Schramm Alexander10,Rehbock Christoph1,Barcikowski Stephan1ORCID

Affiliation:

1. Technical Chemistry I and Center for Nanointegration Duisburg-Essen (CENIDE) University of Duisburg-Essen 45141 Essen Germany

2. West German Proton Therapy Centre Essen (WPE) 45147 Essen Germany

3. West German Cancer Center (WTZ) 45147 Essen Germany

4. Department of Physics TU Dortmund University 44227 Dortmund Germany

5. German Cancer Consortium (DKTK) 45147 Essen Germany

6. Department of Particle Therapy University Hospital Essen 45147 Essen Germany

7. Department of Neurosurgery and Spine Surgery University Hospital Essen 45147 Essen Germany

8. DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ) University Hospital Essen 45147 Essen Germany

9. Pediatrics III Pediatric Oncology and Hematology University Hospital Essen 45147 Essen Germany

10. Laboratory of Molecular Oncology Department of Medical Oncology West German Cancer Center University Hospital Essen Essen Germany

Abstract

AbstractGold nanoparticles (AuNPs) are currently the most studied radiosensitizers in proton therapy (PT) applicable for the treatment of solid tumors, where they amplify production of reactive oxygen species (ROS). However, it is underexplored how this amplification is correlated with the AuNPs’ surface chemistry. To clarify this issue, we fabricated ligand‐free AuNPs of different mean diameters by laser ablation in liquids (LAL) and laser fragmentation in liquids (LFL) and irradiated them with clinically relevant proton fields by using water phantoms. ROS generation was monitored by the fluorescent dye 7‐OH‐coumarin. Our findings reveal an enhancement of ROS production driven by I) increased total particle surface area, II) utilization of ligand‐free AuNPs avoiding sodium citrate as a radical quencher ligands, and III) a higher density of structural defects generated by LFL synthesis, indicated by surface charge density. Based on these findings it may be concluded that the surface chemistry is a major and underexplored contributor to ROS generation and sensitizing effects of AuNPs in PT. We further highlight the applicability of AuNPs in vitro in human medulloblastoma cells.

Funder

European Regional Development Fund

Mercator Research Center Ruhr

Publisher

Wiley

Subject

General Chemistry,Catalysis,Organic Chemistry

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