Therapy-Related Investigations On the DNA Degrading Effect of Noble Metal Nanoparticles in Proton Therapy Using Liquid and Gel-Based Phantoms
S Zwiehoff1*, A Hensel2, C Behrends3,4,5, C Rehbock1, C Baeumer3,4,5,6, S Knauer2, B Timmermann3,5,6,7,8, S Barcikowski1, (1) University of Duisburg-Essen, Technical Chemistry I, Essen, DE, (2) University of Duisburg-Essen, Molecular Biology II, Essen, DE, (3) West German Proton Therapy Centre Essen, Essen, DE, (4) TU Dortmund University, Department of Physics, Dortmund, DE, (5) University Hospital Essen, West German Cancer Centre, Essen, DE, (6) German Cancer Consortium, Heidelberg, DE, (7) University of Duisburg-Essen, Faculty of Medicine, Essen, DE, (8) University Hospital Essen, Department of Particle Therapy, Essen, DE
Presentations
TH-D-202-5 (Thursday, 7/14/2022) 11:00 AM - 12:00 PM [Eastern Time (GMT-4)]
Room 202
Purpose: Biocompatible noble metal nanoparticles (NPs) can act as sensitizers for enhanced tumor tissue damage in proton therapy, a phenomenon widely believed to be correlated to the formation of reactive oxygen species (ROS), causing damage to tumor DNA. However, the underlying mechanisms are poorly understood, especially the effect of the distance between NPs and DNA and how stabilizing ligands interfere with the process. Here we used ligand-free platinum nanoparticles (PtNPs) in solution as well as hydrogel phantoms: I) Co-incubated with plasmid DNA, II) Conjugated to DNA via polyethylenimine (PEI), and III) Stabilized with serum proteins in blood plasma to closely match in vivo conditions. Hydrogel phantoms and solutions were irradiated with protons and DNA damage was analyzed using a DNA cleavage assay based on gel electrophoresis.
Methods: Surfactant-free PtNPs produced through laser ablation in phosphate buffer saline were dispersed in water and gel phantoms. The hydrogel phantoms and solutions contained different concentrations of PtNPs, electrolytes, and bovine serum albumin (BSA). In addition, plasmid DNA and PEI were added in different concentrations and molecular ratios. Proton irradiation of the phantoms was conducted with different physical doses. The DNA cleavage was investigated using agarose gel electrophoresis.
Results: The ligand-free PtNPs possess a monomodal narrow size distribution with a mean diameter of 10 nm. Stabilization of the colloid with BSA during the addition of physiological salt concentrations was successfully achieved. The high dispersion of NPs in the gel was verified by confocal microscopy. Initial proton irradiation experiments could verify the suitability of the selected concept, showing more efficient DNA cleavage and particle surface-related ROS formation in the presence of the PtNPs.
Conclusion: The presented concept could unravel the complex mechanisms underlying the function of noble metal NPs as sensitizers, thereby paving the way for more efficient proton therapy in the human body.
Funding Support, Disclosures, and Conflict of Interest: This work was supported by the MERCUR-Stiftung graduate school 'Praezisionsprotonentherapie - Praxisbezogene Physik und Chemie an der Schnittstelle zur Medizin' (grant number St-2019-0007). Furthermore, the authors acknowledge the European fund for regional development (EFRE) within the project SYNGOPRO for financial support.
Keywords
Tissue Equivalency, Lasers, Protons
Taxonomy
TH- Radiobiology(RBio)/Biology(Bio): RBio- Particle therapy- Protons
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