CHEMICAL PAPERS, sa.11, ss.7187-7196, 2023 (SCI-Expanded)
Glioblastoma (GBM) is a type of the central nervous system malignancy and considered as the most lethal and aggressive primary brain tumor. Adjuvant radiotherapy (RT) along with temozolomide (TMZ) is considered as the standard treatment regimen for GBM. However, implementation of RT in tumor suppression is frequently accompanied by several side effects. Additionally, dose limitation and radioresistance are other major drawbacks associated with radiation therapy. To this end, nanoradioenhancer/or nanoradiosensitizer based on high-Z metallic elements has emerged as a powerful treatment modality in GBM therapy. In this study, CuFe2O4 decorated with BSA nanoplatforms (CuFe2O4 @BSA) was fabricated to improve the theraputics potential of RT through sensitizing the U-87 GBM cells to X-ray radiation. The characterization techniques such as FTIR, XRD, EDS and UV-Vis spectroscopy confirmed successful fabrication of CuFe2O4 @BSA radioenhancer, while also TEM images indicated the prepared nanoradiosensitizers are uniform, homogenous, and spherical with an average size of about 5 nm. In vitro hemocompatibility and cytocompatibility of developed CuFe2O4 @BSA nanoradiosensitizers were also investigated by hemolysis and MTT assay, respectively. The merits of CuFe2O4 @BSA nanoplatforms in sensitizing the U-87 cells to the ionizing radiation were also exploited using intracellular ROS generation and MTT assay. It was found that CuFe2O4 @BSA nanoradiosensitizers did not cause any deleterious effects on primary human umbilical vein endothelial cells (HUVEC) of which the cell viability of all treated group was beyond 95%, endorsing the cytocompatibility and safety of these nanoplatforms for further assessment. Hemolysis assay also confirms the biosafety of CuFe2O4 @BSA nanoradiosensitizers, exhibiting no significant toxicity against human red blood cells in which the degree of hemolysis was less than 4%. In vitro cancer radiotherapy also demonstrated that the cell viability of U-87 GBM was considerably decreased once co-modality of X-ray and CuFe2O4 @BSA nanoradiosensitizers were used simultaneously. Radiosensitizing ability of these nanoparticles was also proved by intracellular ROS generation, of which implementation of CuFe2O4@BSA nanoradiosensitizers upon X-ray irradiation resulted in superior ROS production. Overall, these findings provide vital evidence for applicability of prepared CuFe2O4 @BSA nanoradiosensitizers in killing the primary brain tumor cells specifically GBM.