Research On A Ferrite Nano-organic Free Radical Generator In Tumor Diagnosis And Treatment

More and more effective methods for diagnosis and treatment have been developed because malignant tumors damage people's health seriously.Surgical resection,chemotherapy and radiotherapy are common tumor treatment methods,but they all have lots of limitations which could cause serious damages to normal cells.In view of the high concentration of H₂O₂in tumor cells,the treatment strategy generating reactive oxygen species by H₂O₂from cells to destroy the oxidative balance in the cell,thereby causing the cell to undergo apoptosis.Tumor cells have a strong ability to regulate the intracellular environment,the way that apoptosis triggers cell death is single,which is usually difficult to achieve satisfactory therapeutic effects.Meanwhile the acidic environment and high GSH(glutathione)concentration in tumor cells also have attracted people's attention.Some treatment strategies triggered by p H response or GSH and have achieved certain expected results.However,tumors are not simply stacked by tumor cells.Tumor cells,intercellular substance,immune and inflammatory cells,capillaries,etc.together constitute the tumor microenvironment(TME).Due to the secretion of related cytokines in the environment,they constitute the characteristics of hypoxia,slight acidity,and immunosuppression.Which improves tumors in body to grow,migrate and infiltrate rapidly.Combined with the characteristics of TME,suggesting that some treating tumor methods could be made to strengthen the effect of the tumor treatments.We prepared a kind of ferrite nanoparticles(MNPs),modified with phospholipid PEG to improve water solubility.The external alternating magnetic field is enough to make the local temperature rise rapidly,so that can physically kill the tumor cells.This method is not only limited to the penetration depth of the tumor,but also add the effect of therapy,which related tothe therapeutic effect is related to the time of the magnetic field,the power of the instrument and the concentration of the material.Under the action of acidity and glutathione,the MRI imaging ability of nanoparticles changed.It was found that iron ions were released in the reaction with GSH.As an organic peroxide,m-chloroperoxybenzoic acid(mCPBA)is often used as an oxidant in organic synthesis.It also decomposes in an acidic environment.Under the mediation of ferrous ion(Fe²⁺),it can quickly decompose to produce organic free radicals.The production of organic free radicals affects the redox balance in cells.Therefore,mCPBA was loaded into MNPs to prepare MNPs-mCPBA.In TME,GSH can reduce the iron ions in MNPs to Fe^2+,and mCPBA can undergo a Fenton-like reaction under the mediation of Fe²⁺,and rapidly generate a large number of organic free radicals.Co-incubated cells detected obvious cell DNA damage,increased reactive oxygen species(ROS)and lipid peroxides(LPO),decreased GPX-4 enzyme activity,and CRT eversion.This indicates that the damage to tumor cells includes not includes apoptosis but also iron death.It can activate the cellular immune system.Buy the way,at the animal level,combined therapy with anti PD-L1antibody significantly enhances the tumor suppressive effect.