Preparation And Functional Studies Of Acyclic Cucurbituril Ion Probe And Cyclodextrin Photosensitive Micelles

The recognition and assembly techniques of supramolecular chemistry have been actually applied in modern medicine in areas such as bioimaging,medical diagnosis,and drug delivery.Designing supramolecular based fluorescent probes with targeted delivery vehicles by modification of macrocyclic molecules to render them unique optical and chemical properties has greatly advanced their applications in biomedicine.Acyclic cucurbit[n]uril,as emerging macrocyclic host molecules,have become a research hotspot for fluorescent probes in medical diagnosis due to their large and tunable C-shaped cavities,good aqueous solubility,and easily modified aromatic side walls.Cyclodextrins,as a class of cyclic oligosaccharides,have become the first choice for constructing drug delivery vehicles because of their good biocompatibility and low toxicity.Based on the advantages of acyclic cucurbit[n]uril and cyclodextrins in medical diagnosis and therapy,the following two aspects were studied in this paper.（1）A novel low-toxic fluorescent probe（Py-ACB）based on acyclic cucurbituril and pyrene was designed and synthesized.Py-ACB exhibits high selectivity and sensitivity to Fe³⁺by inducing reverse photo-induced electron transfer（reverse PET）from pyrene units to the carbonyl oxygen atoms through its coordination with Fe³⁺to induce fluorescence quenching in excimer emission.The stoichiometry of the coordination of Py ACB to Fe³⁺was determined to be 1:1 using Job’s curve,and the binding constants and detection limits of Py ACB and Fe³⁺obtained from fluorescence titration experiments were 9.26×10⁴ M^-1 and 2.51×10^-8 M.The competitive experiments showed that Py-ACB still exhibited specific recognition to Fe³⁺in the complex environment in the presence of metal ions and amino acids.More importantly,py ACB can detect Fe³⁺inside living cells by bioimaging because of its low cytotoxicity and high fluorescence emission intensity inside living cells.（2）Based on triethylenetetramine cyclodextrin（TETA-β-CD）and porphyrin-carboxylic acid derivative（TPPC6-SS-COOH）,an amphiphilic compound TPPC6-SS-CD was designed and synthesized,which can self-assemble to form supramolecular micelles in aqueous solution.The micelle is photosensitive and can induce the generation of reactive oxygen species（ROS）to exert photodynamic therapy（PDT）effect.The successful synthesis was verified by ¹H NMR,HR-MS and FT-IR.The chemotherapeutic drug etoposide（EPS）was encapsulated into the nano-micellar cavity.The drug loading of the nano-micellar was up to 15.2%as determined by UV-vis,and the effective release of porphyrin photosensitizer and EPS was achieved under the action of GSH.MTT assay demonstrated the excellent phototoxicity of the drug-loaded micelles.The mitochondrial targeting ability of the nanomicelles was confirmed by observing their uptake and co-localization by laser confocal microscopy.