Study On The Release And Aggregation Behaviors Of Guest Molecules Loaded In PH-sensitive Micelles In Cells

With the rapid development of nanoscience and modern medicine, the applications of smart responsive polymeric nanocarries have been of great importance on the regulation of drug release rate, reducing the administration frequency, decreasing the side effect and toxicity of drugs, improving drug bioavailability and other aspects. Researches on the release and aggregation behavior of guests loaded in smart responsive polymeric nanocarries are of great importance in exploring supramolecular chemistry inside cells and leading to new processes or materials at the interface of chemistry and biology. Based on this we use the advantages of smart responsive polymer nanocarriers have been developed to study the release and aggregation behaviors of the guest molecules loaded in them inside cells. The main contents of this paper are described briefly as follows:⒈ The PEG modified poly(β-amino ester)s graft copolymers with pH-sensitive property weresynthesized via Michael addition.Thestructureand molecular weightofthecopolymers were characterized by 1H NMRandGPCmeasurements.Some important physiochemical properties such as micellesize and morphologieswere investigated by combiningdynamic light scattering(DLS) and transmission electron microscope(TEM).The pH-sensitive property was investigated via pyrene fluorescence experiments. Nile Red(NR) release experiments proved micellesdissociatedin acidic conditions,and DOX was selected as model drug toappreciate pH-triggered drug release and release dynamics of thecopolymer micelles. Near-infrared fluorescence squaraine(SQ) dye as a built-in PAT reporter molecule was loaded into the hydrophobic core of micelles, and the time-dependent photoacoustic signals in tissue-mimic phantoms containing SQ treated cells reflected the drug release process in lysosomes, which were further validated by cell-based confocal fluorescence microscope, proving that we first utilized PAT imaging to monitor the drug release in cells.⒉ At pH 7.4, the bis(pyrene) fluorescent molecules(BPs) monomer loaded pH-sensitive micelles(fluorescence quenching) were prepared. At p H 5.0, the fluorescence spectra data showed that the micelles dissociated, the BPs were released and aggregated into nanoaggregates in situ with enhanced fluorescence.Some important physiochemical properties such as micellesize and morphologieswere investigated by DLS andTEM. Colocalization data and time-dependent fluorescence experiments of cells showed that micelles entered cells and accumulated in lysosomes via endocytosis. The micelles dissociated due to the acidic intracellular lysosome environments, then the BPs were released and self-assembled into nanoaggregates in situ with enhanced fluorescence. Fluorescence spectroscopy of cells and the TEM data of lysed cells further characterized the BPs aggregates in situ, thus achieving the study of intracellular BPs self-assembly in situ.