Studies On The Combination Treatment Of Hyperbaric Oxygen With Temozolomide-loaded Porous Silicon Nanoparticles For Glioma

Hypoxia is a critical hallmark of solid tumors and involves with drug resistance,enhanced cell survival,proliferation and metastasis.The treatment of solid tumor could be markedly enhanced if the tumor hypoxic environment could be relieved.The purpose of this study was to use hyperbaric oxygen(HBO)combined with nanolized temozolomide to explore the treatment of glioma.The main works are as follows:The porous silicon nanoparticles were obtained by using anodic electrochemical corrosion method,and the porous silicon nanoparticles with fluorescence properties were obtained by ultrasonic for 16 hours or more.The porous silica nanoparticles had the porous adsorption capacity of TMZ.The nanoparticles were characterized by dynamic light scattering and transmission electron microscopy.The hydrodynamic diameter of Psi was 103.7 nm and the zeta potential was-18.8mV.The hydrodynamic diameter of TMZ/Psi was 117.3 nm,and the zeta potential was-17.6 mV.UV spectrophotometer was used to detect the drug-loading content of TMZ and its in vitro cumulative release behaviors.The results showed that 0.373 mg TMZ could be loaded in 5mg Psi and in vitro cumulative release of TMZ was completed within 24 h.In vitro cell experiments showed that intracellular imaging of psi nanoparticles could be achieved by autofluorescence of porous silicon.It was proved that Psi nanoparticles could be taken up by cells.The killing effects of nano-drugs on C6 glioma cells at different oxygen concentrations was studied.The results showed that HBO treatment could overcome the drug-resistance of tumor cells in hypoxic conditions,and TMZ could lead to cell cycle arrested at the G2 phase,which inhibited the proliferation of C6 cells.Anti-tumor effects of the nanoparticle was evaluated in vivo.The C6 glioma subcutaneous tumor model was established.The antitumor effect was studied by TMZ/Psi combined with hyperbaric oxygen therapy on day 8 post inoculation of tumor cells.There were seven groups in this study,group Saline,group Psi,group TMZ/Psi,group HBO,group TMZ+HBO,group TMZ/Psi+HBO.The results showed that anti-tumor activity of TMZ / Psi + HBO was the best,and the rate of tumor inhibition was up to 84.15%,which indicated the anti-tumor activity of HBO treatment combined with TMZ / Psi.In summary,the application of nano-drug TMZ/Psi combined with HBO showed perfect therapeutic effects on glioma,and the possible mechanism was to overcome hypoxic environment in the tumor tissue and sensitize tumor cells to TMZ,which enhanced anti-tumor effects of TMZ.Therefore,HBO treatment combined with nano-drugs maybe a potential way to treat gliomas and other tumors.