Construction Of Erythrocyte Membrane Modifying Nano-Drug Delivery System And Anti-Osteosarcoma Treatment

Objective:Chemotherapy is a primary treatment method for osteosarcoma.Although this treatment can prolong the life of some patients,its strong side effects can severely influence their quality of life.At the same time,the existed medical nanotechnologies（such as drug-carrying liposomes,controlled-release polymer systems,long-life-cycle PLGA-PEG nanoparticles,si RNA polymerized nanoparticles,and various inorganic/organic nanoparticles.）limit their application in tumor therapy because of their high immunogenicity and low biocompatibility.Therefore,it’s utmost important to develop a nanodrug system with high biocompatibility,high efficacy and safety,and specific tumor tissue targeting.Methods:An anti-osteosarcoma drug delivery that is based on nanocarrier is a possible way to solve the problems associated with current medical nanotechnology.In this study,a new anti-osteosarcoma nanocomplex,vascular endothelial growth factor ligand-RBC zoledronic acid-calcium ions/doxorubicin（V-RZCD）,was designed and constructed.It is composed of two parts:（1）a core（ZCD）,in which calcium ion(Ca²⁺)and zoledronic acid（ZA）form a metal-organic framework loading with doxorubicin（DOX）,and（2）a shell（V-R）,erythrocyte membrane nano capsule modified by a vascular endothelial growth factor（VEGF）ligand.The effect and mechanism of anti-osteosarcoma of V-RZCD were further verified through in vitro and in vivo experiments.Results:In this study,a new type of multi-functional nano-drug system（V-RZCD）was constructed.This system uses a carrier that is formed by ZA and Ca²⁺loading with DOX as a nano-core and uses VEGF-modified erythrocyte membrane as a nano-shell.V-RZCD targets osteosarcoma cells under the guidance of the VEGF ligand and escapes immune recognition under the camouflage of the erythrocyte membrane.The metal-organic framework of ZA and Ca²⁺in V-RZCD not only acts as a drug carrier,but also induces an acid response to release at the tumor site.The chemotherapeutic drug,DOX,loaded with V-RZCD,exhibits an anti-tumor effect and can monitor the accumulation of drugs at the tumor site via red fluorescence.The results of vitro and vivo experiments show that V-RZCD has specific targeting and selective accumulating in the tumor site after systemic administration.Conclusion:V-RZCD can evade the monitor of immune system,target specific tumor tissue,has high drug load,and possesses a certain capacity of anti-tumor.