Design And Synthesis Of Supramolecular Nanoparticles Constructed By Self-Assembly Of Water-Soluble Pillar[5]arene

Objectives:1.To investigate the proliferation inhibitory effects of perillyl alcohol,thymol,dihydroartemisinin,and traditional anti-tumor drugs DOX/GEM on MCF-7 cells,SMMC-7721 cells,MGC-803 cells,and PC-3 cells and the inhibitory effects of perillyl alcohol,thymol,and dihydroartemisin in combination with DOX/GEM on these cancer cells.2.To prepare supramolecular nanosystems based on water-soluble pillar[5]arene and guest molecules of perillyl alcohol,thymol and dihydroartemisinin prodrugs for traditional anti-cancer drug delivery.3.To prepare a self-assemlbled supramolecular nanosystem with near-infrared emission based on water-soluble pillar[5]arene and DCM fluorescent probe for real-time monitoring the release of anti-cancer drugs.Methods1.The cytotoxicity of perillyl alcohol,thymol,dihydroartemisinin,DOX and GEM on MCF-7 cells,SMMC-7721 cells,MGC-803 cells,and PC-3 cells were measured by MTT method,and then determined the cytotoxicity of the above drugs when combining with DOX/GEM.2.The carboxylated water-soluble Pillar[5]arene(WP5)host molecule and perillyl alcohol guest molecule(G1),thymol guest molecule(G2)and dihydroartemisinin guest molecule(G3)were synthesised,then constructed supramolecular nanosystems based on host-guest chemistry.The structure of the host and guest is characterized by NMR and HRMS,the optimal complex ratio and the best molar ratio between the host and guest were determined by ultraviolet spectrometry,and the particle size of the supramolecular nanosystem was determined by particle size analyzer.3.Constructed a supramolecular nanosystem based on WP5 and near-infrared fluorescent probe(G4).These synthesized compounds were characterized by NMR and HRMS.Results1.Perillyl alcohol,thymol,and dihydroartemisinin showed certain inhibitory activity on MGC-803 cells,SMMC-7721 cells,MCF-7 cells,and PC-3 cells,then combined with DOX/GEM,stilly showing synergistic anticancer effect.2.The host molecule WP5 and the guest G1 were synthesized.The host-guest complex self-assembled into a supramolecular nanosystem with a particle size of 225 nm,the optimal host-guest complex ratio was 1:1,and the critical aggregation concentration was 33.1 μM;The host molecule WP5 and the guest G2 were synthesized.The optimal host-guest complex ratio was 1:1,and the critical aggregation concentration was 30.6 μM.The particle size of the supramolecular nanosystem between WP5 and G2 was 245 nm;Designed the supramolecular nanosystem based on WP5 and G3,the compound intermediate DHA-SS was synthesized,then we characterized its structure by NMR.3.Designed a supramolecular nanosystem based on WP5 and G4.Five compounds 4-1～4-5 were synthesized and characterized by NMR and MS.Conclusion1.Perillyl alcohol,thymol,and dihydroartemisinin showed a certain proliferation inhibitory effect on MCF-7 cells,SMMC-7721 cells,MGC-803 cells,and PC-3 cells.Moreover,these compounds showed a time-dose dependence,in which the anti-tumor activity of dihydroartemisinin and perillyl alcohol were more obvious than thymol,and when combined with DOX/GEM,inhancing the anti-tumor activity of the latter.2.WP5 and G1/G2 can self-assemble to a supramolecular nanosystem in a ratio of 1:1 in water.