Study On The Inclusion Of Supramolecular Host Molecules And Curcuminoid And Their Anti-tumor Activity

Supramolecular host molecules have a specific hydrophobic cavity,and it can interact with many small organic molecules through host-guest interactions to form inclusion complexes of supramolecular host compounds.Therefore,they are used in food,medicine,environment,etc.As a small natural molecule,curcumin has many drug activities such as anti-inflammatory,anti-bacterial and anti-tumor.However,due to its poor water solubility,easy deterioration,poor biocompatibility and other shortcomings,it cannot be widely used in daily life.In this paper,two supramolecular host compounds----β-CDP,pillar[5]arenes were used to prepare host-guest inclusion with curcumin.And we had designed and manufactured some anti-tumor drug inclusion compounds.This paper is mainly composed of the following three parts:1.Preparation,Characterization and Anti-tumor Effect of Cur-β-CDPCur-β-CDP was prepared by grinding method.And Cur-β-CDP was characterized by FT-IR,UV-vis,1H NMR and other methods to prove that the preparation of Cur-β-CDP was successful.The Boltzmann-Hamel method and the Job plot method were used to confirm that the molar ratio of Cur and β-CDP was 1:1,and the calculated KD was 6.4×10-3 mol L-1.The complex inclusion efficiency of Cur-β-CDP calculated by TGA is 100.4%.The Cur-β-CDP was also studied by CV,and the diffusion coefficients of the oxidized and reduced states of Cur-β-CDP were 7.94×10-8 cm2 s-1 and 9.91 ×10-8 cm2 s-1,respectively.The Ed of Cur-β-CDP was calculated to be 37.36 kJ mol-1.Finally,cytotoxicity experiment,cell phagocytosis experiment,immunofluorescence experiment and cell scratch experiment were conducted to study its anti-cancer effect.For HepG2 cells,the IC50 of Cur is 32.149 mg L-1.The IC50 of Cur in β-CDP is 28.137 mg L-1.and Cur-β-CDP can greatly inhibit the migration and proliferation of HepG2 cells.2.Preparation,Characterization and Anti-tumor Effect of BDMC-WP5BDMC-WP5 was prepared by wet grinding method.Then BDMC-WP5 was characterized by FT-IR,UV-vis and 1H NMR to prove that BDMC-WP5 was successfully prepared.We used Boltzmann-Hamel method and Job plot method to confirm that the molar ratio of BDMC and WP5 is 1:1,and we calculated Ka=(8.49±2.20)× 104 L mol-1.The complex inclusion efficiency of BDMC-WP5 calculated by TGA is 94.3%.Finally,HepG2 cells were used to study their cytotoxicity and cell scratch test on their anticancer effects.For HepG2 cells,the IC50 of BDMC in BDMC-WP5 was 12.58 mg L-1,and the IC50 of pure BDMC was 14.37 mg L-1.In addition,BDMC-WP5 can effectively weaken the migration ability of HepG2 cells.3.Supramolecular Self-assembly of BDMC and WP5The pillar[5]arene synthesized in the second part was used for self-assembly with BDMC.We adjusted the concentration and days of self-assembly to find the optimal self-assembly conditions.And it was analyzed by TEM,DLS,fluorescence spectroscopy and UV-vis.Finally,we chose the condition that the concentration of both BDMC and WP5 is 300 μmol L-1,cultured for 18 days is the optimal condition.Afterwards,in order to understand the properties of the BDMC-WP5 self-assembly,the pH response experiment and the pH release experiment were carried out.This nanovesicle can control the release of BDMC by adjusting the pH.