Application And Antitumor Properties Of NIR Responsive Composite Nanofibers In Local Drug Delivery

Osteosarcoma(OS)is one of the most common solid tumors.It is a primary malignant tumor that poses a serious threat to children and adolescents.The current treatments for osteosarcoma mainly consist of surgical resection and chemotherapy.In recent decades,surgery and chemotherapy have improved the quality of life of OS patients.However,due to the incomplete removal of the surgical site,patients still face with the risk of tumor recurrence.Long-term use of chemotherapeutic drugs will bring harm to normal tissue cells and systemic drug resistance.Therefore,in order to solve the problem of recurrence and improve the effect of chemotherapy,it is necessary to explore multifunctional biomaterials.Electrospinning nanofibers have good bioadhesion,high drug loading capacity and encapsulation efficiency.Using them as a drug delivery carrier can not only ensure the drug concentration at the target site,reduce the drug dose,but also reduce drug resistance,thereby improving clinical treatment effect.Photothermal therapy has attracted wide attention from researchers due to its selectivity,non-invasiveness and remote controllability.Photothermal therapy has attracted the attention of researchers due to its selectivity,non-invasiveness and remote controllability.In this study,electrospun nanofibers were used as drug carriers,loaded with AIPH,methotrexate,photothermal ink and polypyrrole,respectively,to explore the synergistic therapeutic effects of nanofibers combined with photothermal and chemotherapy.(1)Methotrexate was loaded into polycaprolactone and gelatin nanofibers by electrospinning method,and then polypyrrole(PPy)was polymerized on the surface of the nanofibers as a photothermal agent.The composite nanofibers MTX@PCL-GEL-PPy with synergistic effect of photothermal and chemotherapy were prepared.Cell experiments were used to evaluate the anti-tumor properties of the composite nanofibers MTX@PCL-GEL-PPy.Under the irradiation of near-infrared light,PPy causes local overheating of the fiber,and the release of the chemotherapy drug MTX causes damage to the mitochondrial function,giving full play to the synergistic effect of photothermal therapy and chemotherapy.The material can effectively inhibit the growth of tumor cells,improve the anti-tumor effect,and has broad application prospects in tumor treatment(2)The core-shell structure composite nanofibers with near-infrared response are prepared by coaxial electrospinning.Firstly,spinning solution contains free radical initiator 2,2’-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride(AIPH),photothermal ink(Ink)and phase change material lauric acid(LA)is prepared.Under near-infrared light,Ink absorbs near-infrared light,converts the light into heat,and raises the temperature,The temperature causes LA to melt,and LA changes from solid phase to liquid phase.The AIPH loaded inside the fiber is exposed,and AIPH is rapidly decomposed into reactive oxygen species(ROS)at high temperatures,destroying the microenvironment of tumor cells,and inducing cell apoptosis.The results of in vitro cell experiments such as MTT,LDH and dead/live cell staining show that core-shell nanofibers can avoid premature leakage of AIPH at 37℃.The combination of the phase change material LA and the photothermal agent Ink can control the release of AIPH and reduce its cytotoxicity.The results of DCFHDA and JC-1 staining indicate that the alkyl radicals produced by AIPH can cause mitochondrial dysfunction and lead to cell apoptosis.The prepared material can control the release of ROS and has broad application space in the treatment of osteosarcoma.