Development Of Biomimetic Photothermal PMAA Nanohydrogels For Enhanced Radiotherapy Of NSCLC

BackgroundHyperthermia is one of the most important ways to improve the curative effect of radiotherapy for non-small cell lung cancer(NSCLC).However,thermal efficiency and temperature control of traditional hyperthermia is poor,which limits its clinical use.The application of nanomaterials makes it possible for hyperthermia to improve the curative effect of radiotherapy.However,its clinical application is limited due to its poor targeting and easy to be cleared by the immune system properties.We extract mesenchymal stem cells(MSC)membrane to cover multifunctional nanocarrier biodegradable polymethacrylic acid(PMAA)and photothermal agent Cypate.It can disguise as "self",reduce the immune clearance,and can be delivered to tumor efficiently and accurately,combined with radiotherapy for multiple tumor destruction to improve radiotherapy effect of NSCLC.This study has not been reported at home and abroad,which is of great innovation and research value.MethodWe use the backflow precipitation polymerization method to prepare soft polymethacrylic acid(PMAA)nanoparticles,the complexation reaction to carry photothermal agent Cypate,and cover bone marrow mesenchymal stem cell(MSC)membranes to build the biomimetic photothermal nanoparticles Cyp-PMAA@MSCs.The structure and properties of nanomaterials were characterized by transmission electron microscope(TEM),ultraviolet-visible spectrophotometer(UV-Vis),dynamic light scattering particle sizer(DLS),thermal imager,etc.In vitro,Cell Counting Kit-8(CCK-8)and dual staining of live and dead cells were used to detect cell activity,and laser scanning confocal microscopy(LSCM)was used to detect the targeting property of the materials to lung cancer cells and the extent of DNA damage.In vivo,targeting ability difference between Cyp-PMAA@MSCs and Cyp-PMAA@RBCs was evaluated by imaging system.Thermal imager was used to observe the photothermal effects of the nanomaterials.We recorded the tumor volume,weight of mice and HE staining to observe the treatment effect of mice with lung cancer.ResultsWe successfully prepared Cyp-PMAA@MSCs nanoparticles with high safety,good targeting ability and photothermal effect.1.High safety: In vitro,the cell relative survival rate was 94%;2.Good targeting ability: In vitro,the material was highly enriched in tumor cells,and in vivo,the concentration of Cyp-PMAA@MSCs was 95% higher than that of Cyp-PMAA@RBCs in tumor sites;3.Good photothermal effect: In vitro,the heating effect of Cyp-PMAA@MSCs was 24 times higher than that of the control group.Radiation of near infrared can kill 74% of lung cancer cells,and has no effect to the absorption of X-ray for cancer cells.In vivo,the nanomaterials used in the photothermal treatment not only can make tumor local temperature to 42-43 ?(12 ? higher than the normal saline control group),but combination therapy inhibit the growth of tumor by 88% compared with RT group.The pathological results showed that there were more cell necrosis and apoptosis in combination therapy group.ConclusionCyp-PMAA@MSCs nanoparticles showed good safety,targeting ability and photothermal effect both in vitro and in vivo.The results demonstrated the biomimetic nanodrug delivery system could further enhance the therapeutic effect of radiotherapy and provide a new strategy for improving the clinical efficacy of NSCLC radiotherapy.