Therapeutic Effect Studies Of Temozolomide Nanoparticles Combined With Photothermal Therapy And Hyperbaric Oxygen On Glioma

Glioma is a malignant tumor that occurs mostly in adults.Chemotherapy is not effective in the treatment of glioma.The hypoxic microenvironment and presence of stem-like cells in tumors may be causes of drug resistance.Therefore,it is conductive to improve the hypoxic microenvironment and enhance chemosensitivity of glioma.In this study,porous silicon nanoparticles(PSi)were used to load chemotherapy agent temozolomide(TMZ).Combined with mild photothermal therapy and hyperbaric oxygen therapy,chemotherapy of glioma was expected to be improved for reducing the stemness.The main results of this study are as follows:1.Water-soluble porous silicon with a particle size of about 90 nm was prepared by ultrasonic concentration after anodic electrochemical etching.TMZ/PSi with a particle size of about 150 nm was obtained by physical adsorption method.The drug loading efficiency was determined to be 10% by ultraviolet spectrophotometry analysis.The mild photothermal properties of PSi and TMZ/PSi were validated by near infrared 808 nm laser irradiation.The cumulative release rate of TMZ was about 80% in 24 hours.2.The viability of glioma stem cell NCH-421 K cells and glioma stem-like cell C6 cells under different treatments were detected.It was proved that mild photothermal and hyperbaric oxygen combined with TMZ/PSi sensitize chemotherapy and improve drug efficacy.The glioma stem cell sphere formation was reduced after the combination treatment through the clone formation assay,which indicates the cell stemness was decreased.3.The qRT-PCR and Western Blot were conducted to verify the expression of stemness and hypoxia-related factors in two kinds of cells under different treatments.The expression of stemness markers SOX2,Nestin and hypoxia related factors HIF-1α,VEGF were significantly decreased after the combination treatment.4.The C6 subcutaneous tumor model was established in mice.TMZ/PSi also had mild photothermal properties in vivo,which was necessary for subsequent treatment.The pharmacodynamic evaluation showed that the combination treatment group had better tumor-inhibition effect than any other groups.Ki-67 immunohistochemistry experiment also disclosed that the combination treatment can effectively reduce tumor cell proliferation.The qRT-PCR and immunohistochemical analysis verified the combination treatment could reduce expression levels of stemness markers SOX2,Nestin and hypoxia-related factors HIF-1α and VEGF in tumor tissues.These results proved that combination treatment can amend tumor hypoxia,reduce tumor stemness,synergistically increase drug sensitivity and enhance anti-tumor effect.In summary,mild photothermal therapy combined with hyperbaric oxygen can increase drug sensitivity by reducing the tumor stemness and relieving hypoxic microenvironment,thereby enabling nanomedicine to exert better therapeutic effects.It can be seen that combination of mild hyperthermia and hyperbaric oxygen with nanomedicine is an effective treatment,which provides a potential strategy in clinic.