Construction Of Functional Supramolecular Assembly And Its Application In Cell Labeling And Controlled Drug Release

Supramolecular chemistry is a new frontier subject which is at the intersection of modern chemistry,materials science and life sciences.It is a chemistry that transcends the molecular level and is a discipline in which molecules are assembled into advanced structures through non-covalent forces.In a sense,supramolecular chemistry has played down the boundaries between organic chemistry,inorganic chemistry,biochemistry and materials science.It highlights a supramolecular system with a specific structure and function.The host-guest chemistry is the embryonic form of supramolecular chemistry.There is no absolute boundary or distinction between supramolecular chemistry and host-guest chemistry.The host-guest chemistry mainly studies the structure,properties and interactions of the host molecule and guest molecule.In this paper,we studied the synthesis and properties of the two guest-host systems,calix[4]arene(CX4)/ lucigenin(LCG)and cucurbit[8]uril(CB[8])/ tripeptide(FGG),and explored their applications in tumor detection and drug release in order to expand their related biological application value.The main contents are as follows:1)By operating the in vitro fluorescence quenching titration and fluorescence recovery titration experiments,the binding constant of CX4 and LCG calculated by fitting fluorescence spectrum is much less than the binding constant between CX4 and the polypeptide CPD.It was demonstrated that when CPD was added to a system containing CX4/LCG,CPD will combine with CX4 for displacement of LCG because of the difference of binding constant.This will provide theoretical support for the later intracellular experiments.2)Compared with normal cells,some tumor cells have overexpressed metalloproteinase(MMPs)on the surface of cell membranes.We have used this feature in combination with CX4/LCG assembly to construct supramolecular systems that can specifically detect tumor cells.We first introduced the fluorescence quenched host-guest complex CX4/LCG into the interior of the cell;At the same time,we attached a linker and a negatively charged peptide on the basis of the peptide CPD to form an electrically neutral polypeptide ACPP.The linker could be recognized and cleaved by metalloprotease.When ACPP was incubated with cells containing CX4/LCG,cells that overexpress MMP such as cancer cells,will recognize and cleave ACPP,and the positively charged fragment CPD after cleavage will autonomously get into the cells,displace the LCG and light the cells.This provides a new method for the detection of tumor cells.3)Vesicles have great potential in drug delivery.We combined vesicles with the host-guest system CB[8])/ FGG to construct a supramolecular system that can use CB[8] to stimulate and induce the rupture of drug-loaded vesicles and release the drug.Functional vesicles doped with different concentrations of lipopeptides FGG-DRK-C14 were constructed by using natural phospholipids POPC,DOPC and POPG.Simulation experiments showed that the hydrophobic end C14 of the lipopeptide could be embedded inside the vesicle,and the hydrophilic head FGG could be exposed on the surface of the vesicle;When the host molecule CB[8] was added to the system,CB[8] could interact with FGG to induce the gather and burst of the vesicle.We also used 5(6)-carboxyfluorescein as a drug model molecule to prepare functional vesicles that enclosed drug molecules.After addition of CB[8],increasing fluorescence curves over time were obtained.At this point,we explore the application of functional vesicles in the controlled release and sustained release of drugs.