Preparation Of Thermo-responsive Polymer Composites And Application For Biodetection And Drug Release

Stimuli-responsive polymers have been attracting great interest for the applications in the field of catalysis, detection, biological and medicine, due to their unique feature to respond to small changes in the environmental conditions.In this thesis, a series of well-defined thermal-responsive polymers and specific functionalized polymer-based nanocomposites have been synthesized combined with the advanced polymerization technology of reverse addition-fragmentation transfer (RAFT) polymerization. In addition, random or block thermal-responsive copolymer nanocapsules are prepared using modified RAFT agents via "grafting from" approach of RAFT polymerization, followed by the covalent and non-covalent modification of the nanocapsules surface. The work carried out in this dissertation includes the following four parts:(1).In the work, the preparation of fluorescent nanohy-brids with core-shell structure and metal-enhanced fluorescence (MEF) effect is presented. The fluorescent core-shell nanohybrids have been prepared using silver nanoparticles (AgNPs) as cores and fluorophore tethered thermoresponsive copolymers with tunable lower critical solution temperature (LCST) as shells. Due to the presence of the active groups of RAFT agent and facilitated modification, the modified RAFT agent (CETP-RB) is synthesized through the esterification reaction between the carboxylic acid group of the RAFT agent (CETP) and hydroxyl group of modified rhodamine B. RAFT polymerization provides well-control over the molecular weight and the molecular weight distribution of the polymeric material. Therefore, a series of fluoresent thermal-responsive copolymers with different LCSTs are synthesized by manipulating the feed ratio of OEG to DEG-A using modified CETP-RB as chain transfer agent. Dithioester or trithiocarbonate groups can be attached onto the surface of Au or Ag nanoparticles via strong Au-S or Ag-S coordination. What’s more, the RAFT agents CETP-RB have trithiocarbonate terminal moieties, which can be employed to graft synthesized fluorescent copolymers onto the surface of Ag nanoparticles. The results also reveal that the fluorescent nanohybrids would exhibit maximal MEF when the polymerization degree is tuned to 350. In addition, as the polymer is the "bridge" to link the fluorophores and Ag nanoparticles, when the temperature is below or above the LCST of fluorescent copolymers, the thermal responsive copolymers disperse well or shrink. This behavior arouses the distance variation of fluorophores to Ag nanoparticles, resulting in the changes of fluorescence intensity. Therefore, the dynamics phase transition process of copolymer grafted on to AgNPs can also be investigated in aqueous medium using the MEF effect.(2). The design and fabrication of stimuli-responsive drug delivery systems with the properties of controlled drug release and subsequent dissociation of drug carriers is still the research hot. Herein, the preparation of thermo-responsive drug carriers with a self-destruction property is presented for controlled drug release, which are prepared by introducing the temperature-responsive copolymer poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-co-AM)) and drug molecules into SiO2 during NP growth at room temperature. According to the thermal-responsibility property of copolymers, the drug release of SiO2 hybrid carriers with or without thermal treatments has been investigated. The results have shown that the amount of drug with thermal treatments is more than that without thermal treatments. In addition, the resulting drug-loaded nanoparticles exhibit faster drug release in an acidic environment (pH 5) than in a neutral one. What’s more, the decomposition of the drug carriers into small fragments should benefit their fast excretion from the body. The controlled drug release of drug molecules and the self-decomposition of the drug carriers are successfully characterized by using TEM, UV-vis spectroscopy and confocal microscopy. Together with the low toxicity and excellent biocompatibility of the copolymer/SiO2 composite, the features of controlled drug release and simultaneous carrier self-destruction provide a promising opportunity for designing various novel drug-delivery systems.(3). On the basis of high load rate and low toxicity of polymeric nanocapsules, a NIR-and GSH-triggered GO sheets wrapped thermoresponsive polymeric nanocapsule carrier with photothermal effect and simultaneous self-degradable property for both photothermal therapy and chemotherapy has been fabricated. First, the SiO2@thermal responsive copolymer nanoparticles are synthesized by "grafting from" reversible addition-fragmentation chain-transfer (RAFT) polymerization of N-Isopropyl acrylamide (NIPAM) and acrylamide (AM) in the presence of N,N’-bis(acryloyl)cystamine as crosslinker with RAFT agent modified SiO2 as chain transfer agent. Then the polymeric nanocapsules are obtained by the removal of SiO2 template. After encapsulation of the anti-cancer drug, GO wrapped polymeric capsules are fabricated by electrostatic interaction between negative charged GO and positive charged polymer. GO sheets can not only act as the gatekeepers preventing pre-release of drugs, but also as photothermal agents for effective local temperature increase under NIR irradiation to kill cancer cells, due to their unique 2D structure and NIR photothermal effect of GO sheets. In addition, GSH can break the disulfide bonds on crosslinker, so the DOX loaded capsule@GO nanocarriers can degrade to become GO sheets and line polymers with the assistance of GSH, resulting in rapid release of drug molucules and safe excretion of dissociative carrier fragments from the body. Besides, the cytotoxicity and photothermal effect of complex have been investigated using HeLa cells as cancer model.(4). Using the similar preparation process, the "smart" folate acid (FA) modified thermal-responsive block polymeric nanocapsules. To inhibit the fast degradation of drug carriers resulting in too fast drug release, the small size and non-degradation polymeric nanocapsules have been synthesized for controlled drug release during a longer period. The polymeric nanocapsules with the size of about 100 nm are obtained after the etching of SiO2 templates, such size of which can facilitate the cytophagy of cells and excretion from the body. The polymeric nanocapsules have target ability by the covalent connection of FA onto the surface of capsules. In addition, the nanocapsules encapsulated indocyanine green (ICG) molecules have fluorescent property and NIR absorbing for bioimaging and photothermal therapy. In addition, when the ICG and DOX loaded polymeric nanocapsules are irradiated with NIR light, the volume of the hollow thermal-responsive polymeric nanocapsules diminished leading to the significantly faster drug release, which are mainly attributed to two factors of the thermal-responsive property of polymeric nanocapsules and NIR photothermal effect of ICG. The design and fabrication of multi-functional polymeric carriers are promising for the application in the field of drug release and targeted photothermal therapy.