Study On Preparation And Properties Of Nanomedicine Based On Dendrimers

Dendrimers have unique dendritic structure,monodispersity and abundant surface functional groups,which make dendrimers to become ideal carriers for small drug molecules.However,the commonly used dendrimers have many positively charged groups on their surface,which have obvious interactions with protein molecules and cause significant cytotoxicity.The dendrimers would be cleared from the blood by the reticuloendothelial system.Therefore,it is important that the biocompatibility of dendrimers would be improved by their surface modification using hydrophilic substance.Zwitterionic materials possess strong hydrophilic ability through electrostatic hydration.The resistance to nonspecic protein adsorption and biocompatibility would be improved by modifying the zwitterionic material on the surface of nanoparticles.The surface modification of nanoparticles by zwitterionic materials often reduces the cellular uptake efficiency of nanoparticles by tumor cells.To solve this problem,the amphiphilicity dendrimers were synthesized,where zwitterionic generation two polypropylene imine dendrimer(G2 PPI)was used as hydrophilic segment and N-(2-mercaptoethyl)oleic acid amide was use as the hydrophobic segment.The amphiphilic dendrimers physically encapsulated doxorubicin(DOX)and chlorin e6(Ce6)and assembled into nano drug-loaded micelles(PPIMYC-DOX-Ce6).The results indicated that PPIMYC-DOX-Ce6 micelles effectively encapsulated DOX,achieved controlled release of DOX in weakly acidic environment,didn’t induce aggregation of fibrinogen solution,and had high inhibition rate for HeLa cells.More importantly,both flow cytometry and fluorescence microscopy results indicated that the cellular uptake efficiency of DOX encapsulated in PPIMYC-DOX-Ce6 micelles was higher than that of free DOX,and this rate was only affected by the temperature.This provides a new approach for the development of biocompatible nano drug delivery systems that can efficiently deliver DOX into tumor cells.The biocompatibility of generation five poly(amido amine)dendrimers(G5 PAMAM)can be enhanced by the surface modification of carboxybetaine acrylamide.However,the modified product lacks pH sensitivity.To solve this problem,a pH-sensitive zwitterionic polypeptide(EK-7)and cell penetrating peptide(TAT)were modified on the surface of G5 PAMAM to prepare biocompatible modified dendrimers.Meanwhile,biocompatible modified dendrimer encapsulated platinum nanoparticles were prepared.