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Radiosensitizers can increase cancer-cell susceptibility to ionizing radiation at lower doses. This study tests whether hafnium oxide nanoparticles (HfO2 NPs) combined with an HDAC inhibitor further enhance radiation effects. The combination with irradiation elevates ROS, collapses mitochondrial membrane potential, and increases DNA double-strand breaks, driving apoptosis and reducing clonogenic survival in 2D/3D models, without cytotoxicity in non-cancerous fibroblasts.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/multimodal-radiosensitization-by-hafnium-oxide-nanoparticles-and-hdac-inhibitors-mechanistic-insights/346499/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/multimodal-radiosensitization-by-hafnium-oxide-nanoparticles-and-hdac-inhibitors-mechanistic-insights/346499.png","ImageObject",300,407,{"name":92,"@type":93},"Finn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are radiosensitizers needed in radiotherapy?","Question",{"text":112,"@type":113},"Radiation can harm healthy tissues and tumors may develop radioresistance. Radiosensitizers selectively increase tumor sensitivity to ionizing radiation, enabling effective treatment at lower doses.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What effect does combining HfO2 nanoparticles with an HDAC inhibitor have under irradiation?",{"text":117,"@type":113},"The combination produces significantly higher ROS, markedly reduces mitochondrial membrane potential, and increases DNA double-strand break formation compared with untreated or single-agent-treated cells.",{"name":119,"@type":110,"acceptedAnswer":120},"Did the treatment show toxicity in non-cancerous cells?",{"text":121,"@type":113},"No cytotoxicity was observed in non-cancerous fibroblasts, supporting a cancer-selective radiosensitizing strategy.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},346499,1790126037,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","Nanoscale Advances  \nPAPER  \nCite this: DOI: 10 .1039/d5na00845j  \nReceived 2nd September 2025  \nAccepted 12th February 2026 DOI: 10.1039/d5na00845j[rsc.li/nanoscale-advances](rsc.li/nanoscale-advances)  \nMultimodal radiosensitization by hafnium oxide nanoparticles and HDAC inhibitors: mechanistic insights  \nCsenge Bocz,ab Dra Izabella Adamecz,  a Krisztina Szo}ke,a Blint Pntek,a Em lia Rita Szab,c Rbert Polanek,c Titanilla Szögi,d Andrea Rnavri,e Katalin Hideghty,cf Zoltn Knya,  e Nra Igaz  †*ag and Mnika Kiricsi  †*a  \nRadiation therapy is routinely utilized in cancer treatment, often in combination with chemotherapy, but is limited by collateral damage to healthy tissues and radioresistance of some tumors. Radiosensitizing agents can enhance tumor cell susceptibility to ionizing radiation, allowing effective treatment at lower doses. High-atomic-number metal-based nanoparticles, such as hafnium oxide (HfO2 NP), can locally amplify the impact of ionizing radiation on cancer cells, augment the radiation-triggered generation of reactive electrons and oxygen species (ROS), induce DNA damage, and ultimately lead to cell death. We hypothesized that this effect can be further enhanced by histone deacetylase (HDAC) inhibitors, which maintain the chromatin in a relaxed state and render the DNA more accessible to genotoxic stress. In this study, we found that HfO2 NPs and the HDAC inhibitor, when combined with irradiation, induced significantly higher ROS production, massively reduced mitochondrial membrane potential, and increased DNA double-strand break formation in cancer cells compared to untreated or single-agenttreated cells. These effects led to a marked reduction in colony-forming potential in both 2D and 3D models and induced significant apoptosis. No cytotoxicity was observed in non-cancerous fibroblasts. HfO2 NPs and the tested HDAC inhibitor form a remarkably efficient cancer-selective radiosensitizing combination, where the enzyme inhibitor facilitates the irradiation-induced DNA-damaging potential of the nanoparticles. This outstanding multimodal approach can target radioresistant cancer cells, while not affecting healthy cells, underscoring its potential in a next-generation nanomedicine-based radiosensitizing strategy to attenuate cancer cell growth for an improved therapeutic outcome.  \nIntroduction  \nIn addition to conventional chemotherapy, radiation therapy is a commonly used anti-cancer modality that employs ionizing radiation to reduce the size and the metastatic potential of solid tumors and enhance the efficiency of chemotherapy. Ionizing radiation exerts its effects both directly by damaging the membrane structures and DNA, and indirectly, via the  \naDepartment of Biochemistry and Molecular Biology, University of Szeged, Szeged,  \nHungary. E-mail: [kiricsim@bio.u-szeged.hu](kiricsim@bio.u-szeged.hu); [kiricsim@gmail.com](kiricsim@gmail.com)  \nbNational Academy of Scientist Education, National Biomedical Foundation, Szeged, Hungary  \ncELI-ALPS, ELI-HU Non-Pro􀀁t Ltd, Szeged, Hungary  \ndDepartment of Pathology, University of Szeged, Szeged, Hungary  \neDepartment of Applied and Environmental Chemistry, University of Szeged, Szeged, Hungary  \nfDepartment of Oncotherapy, University of Szeged, Szeged, Hungary  \ngIncubation Competence Centre of the Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged (SZTE IKIKK), Szeged, Hungary. E-mail: [nora.igaz@bio.u-szeged.hu](nora.igaz@bio.u-szeged.hu)  \n† These authors contributed equally to this work.  \ngeneration of reactive oxygen species that induce injury to macromolecules, cellular components, and organelles. However, as ionizing radiation is not speci􀀁c to tumors, radiation therapy can provoke undesired side effects due to its impact on healthy tissues surrounding the tumor. It also carries a secondary risk of potential carcinogenic effects, in particular when high-dose radiation is applied. Therefore, to improve theefficiency of ","cbCaibPdns9vxwCW","https://ap.wps.com/l/cbCaibPdns9vxwCW","pdf",7820245,18,"English","# Introduction\n## Radiosensitization rationale\n## Nanoparticles as radiosensitizers","[{\"question\":\"Why are radiosensitizers needed in radiotherapy?\",\"answer\":\"Radiation can harm healthy tissues and tumors may develop radioresistance. Radiosensitizers selectively increase tumor sensitivity to ionizing radiation, enabling effective treatment at lower doses.\"},{\"question\":\"What effect does combining HfO2 nanoparticles with an HDAC inhibitor have under irradiation?\",\"answer\":\"The combination produces significantly higher ROS, markedly reduces mitochondrial membrane potential, and increases DNA double-strand break formation compared with untreated or single-agent-treated cells.\"},{\"question\":\"Did the treatment show toxicity in non-cancerous cells?\",\"answer\":\"No cytotoxicity was observed in non-cancerous fibroblasts, supporting a cancer-selective radiosensitizing strategy.\"}]","Multimodal radiosensitization by hafnium oxide nanoparticles and HDAC inhibitors - mechanistic insights | PDF",1790061726,45]