Nanoparticle-mediated radiation therapy (NPRT) is an emerging modality for radiosensitization of highly resistant cancers such as brain cancers. This is due to the ability of specific nanoparticles (NPs) to increase physical dose deposition and subsequent direct damage to cells and DNA within their local vicinity, through enhanced generation of reactive oxygen species, ROS. Here, we report the successful use of PEGylated (biocompatible) core-shell quantum dots (QDs) and carbon quantum dots (CQDs) to simultaneously enhance and assess ROS generation while radiosensitizing highly radioresistant brain cancer cell lines: T98G and U87 Glioblastoma cells. Relative peak fluorescence intensity ratio calculations and average intensity comparisons show highly significant (***p<0.001) enhancement of ROS generation, for 5 Gy and 20 Gy irradiation, applied using a Faxitron Cell Irradiator. By quantifying post-radiotherapy cell attachment, proliferation, migration, cell survival and cell death using electric cell-substrate impedance sensing and clonogenic assays, we demonstrate potentially improved in vitro radiotherapeutic outcomes for brain cancer cells radiosensitized using PEGylated CdSe/ZnS QDs and CQDs.

β-apopicropodophyllin (APP), a derivative of podophyllotoxin (PPT), has been identified as a potential anti-cancer drug. This study tested whether APP acts as an an-ti-cancer drug and can sensitize colorectal cancer (CRC) cells to radiation treatment. APP had an anti-cancer effect against the CRC cell lines HCT116, and DLD-1, SW480 and COLO320DM with IC50 values of 7.88 nM, and 8.22 nM, 9.84 nM and 7.757 nM, respec-tively induction of DNA damage. Colonogenic and cell counting assays indicated that the combined treatment of APP and γ-ionizing radiation (IR) showed greater retardation of cell growth than either alone, suggesting that APP sensitizes CRC cells to IR. Annexin V-propidium iodide (PI) assays and immunoblot analysis showed that the combined treatment of APP and IR increased apoptosis in CRC cells compared with either APP or IR alone. Results obtained from the xenograft experiments also indicated that the combination of APP and IR enhanced apoptosis in in vivo animal model. Apoptosis induction by the combined treatment of APP and IR resulted from reactive oxygen species (ROS). Inhibition of ROS by N-acetylcysteine (NAC) restored cell viability and decreased the induction of apoptosis by APP and IR in CRC cells. Taken together, these results indicate that a combined treatment of APP and IR might promote apoptosis by inducing ROS in CRC cells.

: Nanotechnology has expanded what can be achieved in our approach to cancer treatment. The ability to produce and engineer functional nanoparticle formulations to elicit higher incidences of tumor cell radiolysis has resulted in substantial improvements in cancer cell eradication while also permitting multi-modal biomedical functionalities. These radiosensitive nanomaterials utilize material characteristics, such as radio- blocking/absorbing high-Z atomic number elements, to mediate localized effects from therapeutic irradiation. These materials thereby allow for subsequent scattered or emitted radiation to produce direct (e.g., damage to genetic materials) or indirect (e.g., protein oxidation, reactive oxygen species formation) damage to tumor cells. Using nanomaterials that activate under certain physiologic conditions such as the tumor micro-environment can selectively target tumor cells. These characteristics combined with biological interactions that can target the tumor environment allow for localized, radio-sensitization while mitigating damage to healthy cells. This review explores the various nanomaterial formulations utilized in cancer radiosensitivity research. Emphasis on inorganic nanomaterials showcase the specific material characteristics that enable higher incidences of radiation while ensuring localized cancer targeting based on tumor micro-environment activation. The aim of this review is to guide future research in cancer radiosensitization using nanomaterial formulations and to detail common approaches to radiosensization, as well their relations to commonly implemented radiotherapy techniques.