Efficient Active Oxygen Free Radical Generated in Tumor Cell by Loading-(HCONH₂)·H₂O₂ Delivery Nanosystem with Soft-X-ray Radiotherapy.

Lei Xu,Yiran Shao,Chengkang Chang,Yingchun Zhu

doi:10.3390/ma11040596

Abstract

Tumor hypoxia is known to result in radiotherapy resistance and traditional radiotherapy using super-hard X-ray irradiation can cause considerable damage to normal tissue. Therefore, formamide peroxide (FPO) with high reactive oxygen content was employed to enhance the oxygen concentration in tumor cells and increase the radio-sensitivity of low-energy soft-X-ray. To improve stability of FPO, FPO is encapsulated into polyacrylic acid (PAA)-coated hollow mesoporous silica nanoparticles (FPO@HMSNs-PAA). On account of the pH-responsiveness of PAA, FPO@HMSNs-PAA will release more FPO in simulated acidic tumor microenvironment (pH 6.50) and subcellular endosomes (pH 5.0) than in simulated normal tissue media (pH 7.40). When exposed to soft-X-ray irradiation, the released FPO decomposes into oxygen and the generated oxygen further formed many reactive oxygen species (ROS), leading to significant tumor cell death. The ROS-mediated cytotoxicity of FPO@HMSNs-PAA was confirmed by ROS-induced green fluorescence in tumor cells. The presented FPO delivery system with soft-X-ray irradiation paves a way for developing the next opportunities of radiotherapy toward efficient tumor prognosis.

Highlights

Radiotherapy (RT) is still an important and efficient treatment for most patients with clinical tumor [1]
formamide peroxide (FPO) was synthesized in the cavity and the channels of hollow mesoporous silica nanoparticles (HMSNs)-NH2
FPO was synthesized in the cavity and channels of HMSNs-NH2 by the reaction of formamide and hydrogen peroxide (FPO@HMSNs-NH2 ) at 10 ◦ C

Summary

Introduction

Radiotherapy (RT) is still an important and efficient treatment for most patients with clinical tumor [1]. RT can make interstitial fluid generate free radicals (such as O2− , H3 O+ , HO·, H·, etc.) in the human body, and these free radicals react with biological macromolecules, resulting in irreversible. It is highly warranted to strengthen the efficient killing of irradiation on tumor tissues and reduce the damage to normal tissues. The soft X-ray radiation that we developed produces negligible damage to normal tissue, and the devices that excite soft X-ray radiation are less expensive than the conventional RT devices. Oxygen, playing an important role in RT, can combine with the free radicals to generate new and toxic organic peroxide free radicals (ROO·) [4,5]. In order to overcome tumor hypoxia, many researches depend on transporting

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Conclusion