Magnetic Mesoporous Silica Nanoparticles Incorporated with miR-451 Suppress Development of Cervical Cancer and Enhance Radio Sensitization in Cervical Cancer

Cervical cancer (CC) is one of the most common gynecological malignancies with high mortality, threatening female’s health and reducing their life quality. This study evaluated the synergistic effect of magnetic mesoporous silica nanoparticles (MMSNs), miR-451 on radio sensitivity and cell apoptosis in CC. Magnetic mesoporous silica (Fe3O4/SiO2) nanoparticles were prepared and loaded with miR-451. Then the CC cells were treated with Fe3O4/SiO2 nanoparticles, miR-451-loaded Fe3O4/SiO2 nanoparticles (control group) and untreated (blank group). Cell proliferation was determined by MTT assay, while apoptosis and Hoechst were assessed by flow cytometry. As colony formation assay was conducted to evaluate cell sensitivity to radiotherapy, Western blot analysis detected the expression of apoptosis- and radiosensitization-related genes. Iron oxide particles were present inside and outside the SiO2 channel with characteristic peaks for Fe and skeleton of silica. The miR-451-loaded Fe3O4/SiO2 nanoparticles had an obvious absorption peak with drug loading rate and encapsulation rate reaching 6% and 91%. The release content of drugs increased with decreased pH. Of note, combined treatment with miR-451 and Fe3O4/SiO2 nanoparticles significantly decreased cancer cell proliferation and increased apoptosis (34.36±2.31%), compared to control group and blank group. Furthermore, the levels of D0 (1.67), Dq (0.94), N (1.56), and SF2 (0.43) declined in the presence of miR-451-Fe3O4/SiO2 nanoparticles, accompanied with elevation of ATM and γ-H2AX expression. Meanwhile, the treated CC cells had decreased expressions of DNA damage repair related genes ATM and γ-H2AX. MMSNs carrying miR-451 decreased cell proliferation activity and increased apoptosis and sensitized the CC cells to radiotherapy, to improve tissue repairing. These findings may provide a novel insight into pathogenesis of CC.