Construction And Biological Application Of Pillar[5]arene Based Fluorescent Nano Drug Loading System

The combination of supramolecular chemistry and nanotechnology has greatly promoted the development and progress of nanomedicine.In recent years,some new tumor treatment methods based on external stimulation,such as pHotothermal therapy and pHotodynamic therapy,have been developed.However,the best stimulation time can not be mastered,which will affect the therapeutic effect of tumor.Therefore,it is necessary to develop a fluorescent nano-drug delivery system with dual functions of imaging and drug delivery.In view of the unique rigid structure,excellent complexation ability and easy modification performance of pillar[5]arene,the supramolecular nano drug delivery system is constructed based on the pillar[5]arene and anticancer drugs.It is clear that the cavity of pillar[5]arene can directly load the drugs with high spatial potential resistance.The functional modification of pillar[5]arene makes the pillar[5]arene have the dual properties of imaging and drug loading.Based on the interaction between functionalized pillar[5]arene and the host and guest of anticancer drugs,a fluorescent nanodrug delivery system was constructed,and their properties and applications were studied.The details are as follows:1.The complexes were formed by the recognition of the main and guest of water soluble pillar[5]arene(WP5)and the small molecule irutinib(IBR),and the complexes were further self-assembled to form nanoparticles in aqueous solution.The interaction between WP5 and IBR was confirmed by UV,FT-IR,1H NMR,2D NOESY NMR and molecular simulation.TEM showed that the wall thickness of the supramolecular vesicles with a thickness of 14.3 ± 0.08 nm was obtained by the self-assembly of WP5 and IBR.The vesicle has good stability(ζ-potential=-41.2 mV).The stoichiometric ratio of the two was about 1:1.The binding constant k=(2.13± 0.10)×104 M-1 indicates that WP5(?)IBR complex has moderate binding strength.The drug release under different pH conditions was simulated in vitro.The WP5(?)IBR nanoparticles were observed to be pH responsive by drug release curve,which could realize the drug release in cancer cells,and play a therapeutic role.The antitumor activity of WP5(?)IBR nanoparticles was studied by MTT experiment.Compared with the single IBR,the antitumor activity of the nanoparticles to CT26 cells was more significant when CWP5(?)IBR＝CIBR＝1.8×10-5 M.The above research shows that the cavity of pillar[5]arene can directly load the anticancer drugs with high steric potential resistance,which provides the possibility for the construction of supramolecular nano drug delivery system for the pillar[5]arene and other complex structures2.The classical ICT basic unit dansylamide was introduced into pillar[5]arene,and 4C-G ICT probe with good sensitivity to protein microenvironment was synthesized.The fluorescent nano-drug carrier system was constructed based on the host-guest interaction between 4C-G and the anticancer drug regorafenib(REG).The interaction between probe 4C-G and REG was confirmed by UV visible spectropHotometry and 1H NMR and 2D NOESY NMR.The results show that the probe 4C-G and REG form a 1:1 complex by non covalent interaction.TEM images show that the composite is spHerical nanoparticles.4C-G(?)REG nanoparticles can be polymerized and integrated into larger particles in acid conditions,which has better pH response,and 4C-G(?)REG nanoparticles have a higher drug loading rate(89.3%).The results of living cell imaging and MTT analysis showed that 4C-G(?)REG nanoparticles have good anticancer effect and imaging performance on HepG2 cells.3.7-(Diethylamino)coumarin-3-carboxylicAcid(DCCA)was introduced into pillar[5]arene as the ICT basic unit,and a series of ICT probes 3C-B、4C-B、5C-B were synthesized.The 3C-B、4C-B、5C-B of the length of the carbon chain of the bridging unit showed good sensitivity to the protein microenvironment,among which 3C-B had good response to many proteins.Based on the non covalent interaction between 3/4/5C-B and REG,three fluorescent nanodrug delivery systems were constructed.The results of UV and NMR analysis showed that the binding ratio of 3/4/5C-B and REG was no different,but the binding ability and binding attitude of 3/4/5C-B to REG were not same,among which 4C-B could better complex REG.The results showed that the spHerical nanoparticles were formed in the solution by TEM and DLS.Under the condition of acid,3/4/5C-B(?)REG nanoparticles showed the enrichment ability of pH control.The loading rate of 3/4/5C-B(?)REG was over 90%.3/4/5C-B=)REG nanoparticles showed good anticancer activity and live cell imaging performance on HepG2 cells.