title: Nanoparticle-aided external beam radiotherapy leveraging the Čerenkov effect.
abstract: This study investigates the feasibility of exploiting the Čerenkov radiation (CR) present during external beam radiotherapy (EBRT) for significant therapeutic gain, using titanium dioxide (titania) nanoparticles (NPs) delivered via newly designed radiotherapy biomaterials. Using Monte Carlo radiation transport simulations, we calculated the total CR yield inside a tumor volume during EBRT compared to that of the radionuclides. We also considered a novel approach for intratumoral titania delivery using radiotherapy biomaterials (e.g. fiducials) loaded with NPs. The intratumoral distribution/diffusion of titania released from the fiducials was calculated. To confirm the CR induced enhancement in EBRT experimentally, we used 6MV radiation to irradiate human lung cancer cells with or without titania NPs and performed clonogenic assays. For a radiotherapy biomaterial loaded with 20μg/g of 2-nm titania NPs, at least 1μg/g could be delivered throughout a tumor sub-volume of 2-cm diameter after 14days. This concentration level could inflict substantial damage to cancer cells during EBRT. The Monte Carlo results showed the CR yield by 6MV radiation was higher than by the radionuclides of interest and hence greater damage might be obtained during EBRT. In vitro study showed significant enhancement with 6MV radiation and titania NPs. These preliminary findings demonstrate a potential new approach that can be used to take advantage of the CR present during megavoltage EBRT to boost damage to cancer cells. The results provide significant impetus for further experimental studies towards the development of nanoparticle-aided EBRT powered by the Čerenkov effect.
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Medical Physics Program, Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA, USA.
authors.forename: Zi
authors.initials: Z
authors.lastname: Ouyang
authors.affiliation: Medical Physics Program, Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
authors.forename: Sayeda
authors.initials: S
authors.lastname: Yasmin-Karim
authors.affiliation: Medical Physics Program, Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA, USA.
authors.forename: Erno
authors.initials: E
authors.lastname: Sajo
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Medical Physics Program, Department of Physics and Applied Physics, University of Massachusetts Lowell, Lowell, MA, USA. Electronic address: wngwa@lroc.harvard.edu.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Ngwa
mesh_terms: D000072283:A549 Cells; D005240:Feasibility Studies; D006801:Humans; D009010:Monte Carlo Method; D053758:Nanoparticles; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D011878:Radiotherapy / Q000379:methods*; D014025:Titanium / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D017319:Photosensitizing Agents; C009495:titanium dioxide; D014025:Titanium
keywords: EBRT; Titania nanoparticles; Tumor sensitization; Čerenkov