Cell Membrane-inspired Modification Of Dendrimer PAMAM And Its Property Studies

As a unimolecular micelle,dendrimer polyamidoamine?PAMAM?has become one of the research hotspots in biomedical field because of its excellent properties such as small particle size,strong permeability,non-immunogenicity and high transport efficiency.However,there is still a need to improve its biocompatibility and expand its function for further uses.Surface biomimetic modification is an effective strategy to achieve this goal,which has been widely concerned.Taking phosphatidylcholine as the simulation object,two kinds of cell membrane bionic modified PAMAM:cationic phosphodicholine polyamidoamine?PAMAM-PDC?and zwitterionic phosphorylcholine polyamidoamine?PAMAM-PC?were synthesized by modifying the surface of dendrimer polyamidoamine?PAMAM G4?through a phosphorus chemistry method,and their structures,hydrolytic stability and biocompatibility were evaluated.The cationic cell membrane biomimetic dendrimer PAMAM-PDC was firstly synthesized by Atherton-Todd reaction and the zwitterionic PAMAM-PC was obtained through further hydrolyzed,both of them were characterized by ¹H and ³¹P NMR spectra.The results of plasma emission spectrometer?ICP?confirmed that the number of PDC?or PC?on the dendrimer PAMAM surface was 10,and the degree of substitution was 15.6%.Transmission electron microscope?TEM?demonstrated that all of the PAMAM,PAMAM-PDC and PAMAM-PC particles showed spherical nanostructures.In order to research the hydrolytic stability of the phosphorus chemical biomimetic modified PAMAM,cell membrane bionic modified small molecules:phosphodicholine 3-aminopropyltriethoxysilane?APTES-PDC?,cell membrane bionic modified linear macromolecule:phosphodicholine polyvinylamine?PVAM-PDC?and phosphorylcholine polyvinylamine?PVAM-PC?,and cell membrane bionic modified chitosan?CS-PDC and CS-PC?were synthesized by similar methods based on Atherton-Todd reaction.The hydrolytic stability of the biomimetic group was studied by ³¹P NMR spectra tracking.The results showed that the hydrolytic stability of the biomimetic group of the modified cell membrane was related to the degree of substitution of choline,p H value and the molecular configuration of the matrix.It was more stable in acidic and neutral environment than in alkaline,and the hydrolytic stability of the PC group was better than that of the PDC group.For different molecular configuration matrixes in the neutral solution,the order of the hydrolytic stability of the PDC group was APTES-PDC>PVAM-PDC>PAMAM-PDC>CS-PDC,which the hydrolytic stability of the PC group also has the same rule.The biocompatibility of cell membrane biomimetic modified PAMAM was evaluated.However,the exothermic peak of cold crystallization of the freezing bound water was not observed in DSC spectrum.The interaction experiment with BSA showed that the modified dendrimers PAMAM-PDC and PAMAM-PC could reduce the change of protein conformation and improve the thermal stability of BSA.The results of MTT test of cytotoxicity in vitro indicated that the cytocompatibility of biomimetic modified PAMAM-PDC and PAMAM-PC were improved.The results of hemolysis test showed that the modified dendrimer polyamide had good blood compatibility.In summary,two kinds of cell membrane bionic modified PAMAM:cationic phosphodicholine polyamidoamine?PAMAM-PDC?and zwitterionic phosphorylcholine polyamidoamine?PAMAM-PC?were synthesized via Atherton-Todd reaction,which had potential application value in the fields of gene transfer and drug delivery due to the improvement of their biocompatibility.