| In recent years,new cancer cases in our country continue to rise,China’s cancer incidence accounts for a quarter of the world.In many types of cancer,glioblastoma has the characters of high incidence and difficult to cure,easy recurrence,survival period is short,poor quality of life and so on.Faced with such serious situation,researchers need to prepare and develop a new type of anti-tumor targeted nanotherapy delivery system for the treatment of cancer.People usually use the method of chemical conjugate with peptides or other targeting ligand modified in the surface of different nanomaterial carriers to form a tumor targeting nanotherapy delivery system.However,it is often related to the chemical reaction,which we need necessary to take into account the reaction conditions,steps are complicated,as well as the use of the group is available,the purity of the product,the more reaction process the lower yield of the problem.We change the common way of targeted modification,reduce reaction steps,prepare the modular nanotherapy delivery system,modular components with different functions through physical interaction for assembly,successfully avoiding tedious chemical synthesis,which make the preparation of nano-medicine deliver system more convenient and controllable.Firstly,the functional targeting elements are prepared,and then prepare the PGG-PTX delivery system of tumor penetrating peptide modified by physical encapsulation.The system includes RGERPPR peptide modified target element,Polymer and antitumor drugs,which target component is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-RGERPPR(DSPE-PEG-RGERPPR);Polymer has poly glutamic acid(PGA)polymer skeleton and the glutamate branched chain on the skeleton,the anti-tumor drug is paclitaxel(PTX).Glutamic acid side chain is covalently conjugated to the Poly-L-glutamate sodium salt through peptide bond,The PTX is covalently conjugated to the added glutamic acid side chain through ester bond,formation of PGG-PTX.Then PTX and DSPE by hydrophobic interaction.Targeting component of hydrophobic DSPE package into the PGG-PTX.The tumor targeting nano-medicine deliver system is formed by the physical interaction.We take advantage of dynamic light scattering(DLS),high performance liquid chromatography(HPLC),Flow Cytometer(FCM),transmission electron microscopy(TEM)and other instruments and methods to carry out a series of characterizations for RGE-PEG-DSPE/PGG-PTX nanoparticles.The results show:Particle size of around 100 nm,spherical,good dispersion;Stable in phosphate buffer;Slow drug release;Through the qualitative and quantitative test,we can see that the uptake of the drug delivery system by tumor cells and vascular endothelial cells is significantly increased,The drug delivery system has better targeting to tumor.In vitro evaluation of anti glioma activity,the drug delivery system significantly enhanced the inhibitory effect of polymeric nanoparticles on glioma growth in vitro;By intravenous administration,the tumor EPR effect and the role of RGERPPR mediated targeting to the tumor site;The drug delivery system can be used as a targeted delivery of tumor therapeutic drugs,and has a good curative effect in the treatment of glioblastoma.The median survival time of BALB/C glioma in nude mice is prolonged,and the quality of life was significantly improved.The construction of this system can be used for the targeted therapy of glioma under the peptide RGERPPR mediated.It provides a new idea and method for the construction of targeted nanoparticles,and provides the experimental basis for the targeted therapy of glioblastoma.Therefore,this study has potential practical significance and market value,and has good application prospects. |
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