Hollow Mesoporous Silica-based Reactive Oxygen Delivery Nanosystems For Improving Radiotherapeutic Efficacy

Currently,as an adverse prognostic factor in tumor radiotherapy,tumor hypoxia further results in radiotherapy resistance.Therefore,it is highly warranted that reactive oxygen species（ROS）as the radiosensitizers can improve radiotherapeutic efficacy.The experimental results obtained were as follows:（1）In this study,we present the strategy of ROS delivery using hollow mesoporous silica nanoparticles（HMSNs）for tumor therapy by pH-responsive release of ROS in tumor cells and generating free radical to modulate cancer cells death under the soft X-ray irradiation.Formamide peroxide（FPO）as the ROS resource is synthetized by reaction of formamide and hydrogen peroxide at 10℃and enter in cavity and channels of polyacrylic acid（PAA）-coated HMSNs（FPO@HMSNs-PAA）by stirring.FPO release capacity of FPO@HMSNs-PAA will be enhanced in simulated acidic tumor microenvironment（pH 6.50）,while diminished in simulated normal tissue media（pH 7.40）.In vitro,it has been verified that FPO@HMSNs-PAA applied alone has no obvious cytotoxicity.Whereas,the enhanced FPO release in the tumor at acidic pH 6.50 further leads to generate ROS under the soft X-ray irradiation,which can improve radiotherapy treatment.At the same time,the pH-dependent FPO release could lead to obviously lower ROS level of FPO@HMSNs-PAA in tumor at normal tissue pH 7.40 than that in tumor at acidic pH 6.50.（2）An inorganic hydrogen peroxide adduct（4Na₂SO₄·2H₂O₂·NaCl）was synthesized as ROS resource by a simple method.Hollow mesoporous silica（HMSNs）was chosen as the carrier of ROS resource,and chitosan（Cs）was coated on the surface to achieve drug encapsulation and pH-responsive release.Since selected low-energy soft-X-rays have proven to be almost non-toxic to cells,secondary radiation was innovatively proposed in this study to increase the lethality of tumor cells.The results of cell experiments in vitro showed that4Na₂SO₄·2H₂O₂·NaCl@HMSNs-Cs alone had no cytotoxicity.However,after the combination of soft-X-rays,the tumor cells viability was significantly reduced.Also,after the secondary irradiation,cells viability without sample addition is still high,and cells viability cells viability the added sample cells is further reduced.