Supramolecular Assemblies And Biological Applications Based On Water-Soluble Calixarenes

Calixarenes represent one of the most widely studied classes of organic supramolecular hosts,and are described as “macrocycles with(almost)unlimited possibilities” due to their facile modification.Owing to the tunable and fixed molecular skeleton,calixarenes have been regarded as desired multivalent scaffolds to build podand-like receptors,which endow them highly diverse applications in molecular recognition and sensing,self-assembly,catalysis,nanotechnology,and drug discovery.After functional derivatization,calixarenes exhibit good water-solubility and biocompatibility.The cavity inclusion property of water-soluble calix[n]arene is significantly enhanced,since the driving forces are more effective in aqueous media.Benefiting from this,calixarenes are capable of promoting the self-aggregation of aromatic or amphiphilic molecules by lowering the critical aggregation concentration,enhancing the aggregate stability,and regulating the degree of order in the aggregates,which is referred to as calixarene-induced aggregation.A series of calixarene-induced supramolecular amphiphiles have been explored to develop novel strategy for supramolecular assembly and their biological applications have been studied.The major contents of this thesis are as follows:1.The general aspect of the biological application of calix[n]arene was described.The new progress and important achievements on calixarene-induced aggregation were reviewed.2.A phosphatase-responsive supramolecular amphiphilic assembly was fabricated as an operationally targeted drug delivery carrier based on the host–guest complexation of amphiphilic calixarene with adenosine triphosphate(ATP).Remarkably,the complexation of calixarene with ATP lowers its critical aggregation concentration pronouncedly to form hollow spherical nanoparticles.Moreover,the spherical assembly is efficiently responsive to phosphatase that is overexpressed in many tumor cells.3.A novel strategy of ‘‘drug chaperone'' was developed,where drug entrapment was successfully achieved by directly coassembling amphiphilic macrocycles with drugs via electrostatic and hydrophobic interactions.The resulting nanoparticles possess high loading efficiencies and protect drug molecules from alkalization.Furthermore,the coassembly serves as a versatile and multifunctional nano-platform that can be hierarchically decorated in a facile,non-destructive and modular manner benefiting from the intrinsic recognition site of macrocyclic amphiphilie.In cell experiments to validate the drug chaperone strategy,the anticancer activities of free drugs were pronouncedly improved by coassembling with amphiphilic chaperone and further functionalization with targeting ligand.4.A perfect combination has been achieved between naturally occurring liposome and artificially macrocyclic receptor.Possessing long alkyl chains at lower rims,the amphiphilic p-sulfonatocalix[4]arenes can be readily embedded in the liposomal bilayers of zwitterionic phosphoglyceride,making the mixed liposomes a particularly appealing candidate for live cell imaging and targeted delivery.The obtained multifunctional vesicles possess several requisite characteristics for drug delivery purpose:(a)the negatively charged outer shell originating from p-sulfonatocalix[4]arene that can lead to long-term colloidal stabilization in aqueous solution;(b)facile,non-destructive,noncovalent,and modular surface modification using specific host-guest interaction;(c)fluorescent imaging properties through the noncovalent linkage of fluorophores onto the lipid surface;and(d)surface decoration with biologically active ligands capable of specific targeting.5.Photosensitizers show great tendency for self-aggregation in aqueous media,generally leading to quenched fluorescence and lower photosensitizing ability.Herein,we report that amphiphilic anthracene is highly photoreactive after aggregation induced by p-sulfonatocalix[4]arene in water.The formation of a host-guest supramolecular assembly and the photolysis of the anthryl core are identified by UV-vis and NMR spectroscopy,dynamic light scattering,and transmission electron microscopy.Additionally,the assembly exhibited efficient photolysis with visible light in the presence of exogenous photosensitizers.