Construction Of Drug Loading Platform Of Platelet Membrane Bionic Photothermal / Chemotherapy Synergistic Therapy And Its Anti-tumor Effect

Objective: Cancer is listed as the second leading cause of death in the world,with more than 18 million newly diagnosed cases every year.Most of them need to be suppressed by adjuvant chemotherapy or radiotherapy.However,this therapy still causes serious side effects,and it often leads to low survival rate due to indiscriminate drug distribution or radiotoxicity between cancer tissue and normal tissue.In order to enhance the precise therapeutic effect of tumor on the premise of ensuring the safety of organism itself,we designed and established a nano sustained-release platform for the synergistic treatment of cancer by photothermal therapy and chemotherapy with bionic camouflage of platelet membrane.Methods:（1）Preparation and characterization of PLTM-DOX@MPDA nano-carriers.In the experiment,mesoporous polydopamine（MPDA）nanoparticles were prepared.Then the anticancer drug doxorubicin（DOX）was loaded by Schiff base reaction.Platelets（PLT）were extracted from the blood of nude mice by centrifugation,and platelet membranes（PLTM）were obtained by repeated freezing and thawing at low temperature.PLTM-DOX@MPDA nanodrug loading system was prepared by repeated extrusion and ultrasonic treatment.A series of characterization methods were used to prove the successful construction of nano-carriers.（2）To explore the photothermal properties of PLTM-DOX@MPDA nano-carriers,record the temperature changes of different concentrations of PLTM-DOX@MPDA nanocarriers under different power near-infrared laser irradiation,and detect the photothermal conversion efficiency and photothermal stability of PLTM-DOX@MPDA nano-carriers.The drug loading rate and entrapment efficiency of DOX in nano-drug loading system were detected by ultraviolet spectrophotometer.The drug release properties of PLTM-DOX@MPDA nanoparticles under different conditions were also investigated.（3）The anti-tumor effect of nanoparticles in vivo and in vitro was studied by cell experiments and animal experiments.Human breast cancer cell（MDA-MB-231）was used as a tumor cell model to study the targeting,biocompatibility and tumor killing effect of nanoparticles in vivo and in vitro.Results: Transmission electron microscope images confirmed that MPDA nanoparticles were uniform mesoporous spheres.BET results showed that the pore size of MPDA nanoparticles was about 45.57 nm,and dynamic light scattering analysis showed that the particle size of PLTM-DOX@MPDA nanoparticles was about 184 nm.The results of Zeta potential and Western blotting confirmed that PLTM successfully coated DOX@MPDA nanoparticles.The photothermal experimental results show that the nano-carrier has good photothermal performance and photothermal stability,and the photothermal conversion efficiency is as high as 42%.The drug loading rate and entrapment efficiency of DOX were38.63% and 98.86%,respectively.The results of drug release experiments show that the PLTMDOX@MPDA nano-drug loading system has the properties of p H and near-infrared light response.Cell experiments in vitro and in vivo experiments show that the nano-drug loading system has good active targeting,biocompatibility and anti-tumor properties.PLTMDOX@MPDA nano-drug loading system can synergistically inhibit the biological activity of tumor cells by photothermal therapy / chemotherapy.Conclusion: The PLTM-DOX@MPDA nano-drug carriers constructed in this study have excellent biocompatibility,photothermal properties,active targeting and anti-tumor properties.These results show that the nano-platform has great potential in drug delivery and anti-tumor therapy.