Synthesis Of Mesoporous Silica-based Active Oxygen Delivery Nanosystems For Radiosensitization Therapy

Radiotherapy acts as an important role in cancer therapy, but the existence of tumor hypoxic cells causing resistance to radiation, which lower the efficiency of radiotherapy. It has attracted extensive critical attention to radiation sensetizers for improving the efficiency of radiotherapy. In this study, we use active oxygen to improve the efficiency of radiotherapy. Herein, we report oxygen delivery functional materials applied in cancer therapy by using mesoporous silica as carriers. The main results obtained were summarized as follows:(1) Hollow mesoporous silica nanoparticles(HMSNs) were chosen as carriers, sodium percarbonate(SPC) was chosen as the active oxygen resource and was synthesized in the channels and cavity of HMSNs, which were further coated with pH-sensitive PAA to prepare SPC@HMSNs-PAA. The SPC delivery nanosystem helped improve the stability of SPC and control SPC release in tumor acidic microenvironment(p H~6.5), which can provide active oxygen to improve radiotherapy outcome even under low energy X-ray irradiation. The events induce obvious overproduction of reactive oxygen radicals(ROS) to kill cancer cells with significant effect. Meanwhile, no obviously cytotoxicity was observed when SPC@HMSNs-PAA applied alone.(2) Magnetic mesoporous silica nanocomposite(FeOx-MSNs) was prepared by the reaction between potassium ferrate and the template(CTAB) of mesoporous silica nanoparticles. Artemisinin(ART) was chosen as the active oxygen resource. ART@FeOx-MSNs significantly improved the solubility of ART after it was loaded into the as-prepared FeOx-MSNs. The targeted drug delivery system ART@FeOx-MSNs gathered after treated with applied magnetic field. FeOx-MSNs showed good biocompatibility and no obvious cytotoxicity. In vitro studies showed that low-dose ART@FeOx-MSNs can be taken up by ZR-75-30 cells and showed low cytotoxicity. Significant cytotoxicity was observed when combined with low-energy X-ray irradiation. The combination of low-dose ART@Fe Ox-MSNs and low-energy X-ray irradiation led to significantly enhanced intracellular the generation of ROS and increased the killing effect of low-energy X-ray. The overproduction of ROS was demonstrated by the intensity of luminescence, which was induced by the reaction of intracellular ROS with DCFH-DA.(3) SPC@HMSNs-PAA was chosen to transport active oxygen. FeOx-MSNs were transported into cells and trapped in acidic lysosome(pH≤5.0), further produced Fe2+.The Fe2+ catalyzed the produced H2O2 to generate reactive oxygen through Fenton. It showed that the catalytic decomposition of SPC(released by SPC@HMSNs-PAA)by FeOx-MSNs generated more HO? in PBS at pH 5.0 than that at pH 7.4. In vitro studies showed that no obviously cytotoxicity was observed when SPC@HMSNs-PAA and FeOx-MSNs applied respectively, the 24 h cell viability was above 90%, while the SPC@HMSNs-PAA combined with FeOx-MSNs exhibited significantly high cytotoxicity. DCFH-DA was used to investigate the ROS level in cancer cells in vitro. FeOx-MSNs caused an overproduction of ROS by the observation of the increasing intensity of luminescence, further increased the cytotoxicity.