Preparation And Study On Anti-tumor Performance Of Zwitterionic Nano Drug-loaded Micelles

The disadvantages of small molecule chemotherapeutic drugs,such as poor water solubility,low bioavailability,and large toxic and side effects,have brought great pain to the treatment process of cancer patients.Therefore,nano-drug carriers that can effectively alleviate these problems are urgently needed.In recent years,zwitterionic materials have shown excellent biocompatibility and anti-protein non-specific adsorption properties,and the construction of nano-drug carriers based on zwitterionic materials as hydrophilic layers will help alleviate the shortcomings of small molecule chemotherapy drugs.In this paper,two nano-drug-loading systems were prepared based on dendrimers modified by zwitterionic materials and zwitterionic polypeptide(EK7),and their preparation conditions,particle size,anti-protein non-specific adsorption properties,drug Release and anti-tumor properties in vivo and in vitro.The research content of this paper is as follows:(1)In order to solve the shortcomings of small molecule chemotherapy drugs such as low targeting and easy drug resistance.In Chapter 2 of this paper,the second-generation polypropylene imine dendrimer(G2 PPI)was modified by zwitterionic,and the hydrophobic drug paclitaxel(PTX)and targeting peptide c(RGDf C)were modified simultaneously to synthesize the amphiphilic prodrug molecule(PPIMPRC)of the group was prepared.Then the nano drug-loaded micelles(PPIMPRC-DOX)of PPIMPRC loaded with doxorubicin(DOX)were prepared by dialysis.The total drug loading of PPIMPRCDOX is 32.45%,which has a relatively high drug loading.In addition,the hydrodynamic particle size of PPIMPRC-DOX is 93.1 nm,and PPIMPRC-DOX has the ability of charge reversal.PPIMPRC-DOX has good stability in fibrinogen solution.Compared with free DOX,PPIMPRC-DOX has stronger cytotoxicity and higher cellular uptake efficiency in a low p H environment.(2)Aiming at the shortcomings of complex synthesis steps of nano-drug carriers,in Chapter 3 of this article,a zwitterionic polypeptide(EK7)and dodecyl acrylate were linked to synthesize a p H-responsive amphiphilic molecule through a simple click reaction(EKD),EK-D then prepared drug-loaded micelles(EK-D-DOX)by physically embedding DOX.The results show that EK-D-DOX has good aqueous stability and anti-protein non-specific adsorption performance at p H 7.4,but EK-D-DOX will aggregate under the condition of p H=5.5,which is beneficial to its stability in acidic conditions.easier to be taken up by tumor cells.In addition,EK-D-DOX can release more DOX in a slightly acidic environment than at p H 7.4,and the cumulative release of DOX is as high as 75.20% at p H 5.5.More importantly,EK-D-DOX has a better tumor inhibitory effect in vivo than free DOX,and the tumor inhibition rate is 95.7%.EK-D-DOX not only has lower biological toxicity to normal tissues than free DOX,but also has a longer blood circulation time in mice.