Preparation And Application Of Composite Carrier Materials Based On MOFs Or Hollow Mesoporous Silica

Composite material is usually understood as the combination of two or more single materials to realize the complementary functions and collaborative optimization.Composite material can not only integrate the superior merits of both single materials,but remain the main characteristics of the original component materials,relatively.Due to this,composite material has aroused widespread concern and consistent favour of scholars in related fields.Among them,Metal-organic frameworks(MOFs)and Hollow mesoporous silica(HMS)nanoparticles have drawn greater attention in these years due to their multifunctional properties including large surface area,ultrahigh porosity,structural diversity as well as functional groups easy to be modified.However,both of the two materials have some drawbacks,such as poor solvent dispersion and easy to reunite,which limited their further application.These shortcomings can be overcome by surface modification of MOFs and HMS materials through coating or grafting stimulate responsive polymers to obtain composite materials.The composite material can not only improve the dispersion of particles,but respond to pH,light or thermor.Therefore,composite material is widely used in gas adsorption and separation,catalysis,sensors,drug sustained release and immobilized enzyme,etc.Based on the above theories and by virtue of atomic transfer radical polymerization(ATRP),Click chemistry and Post-synthetic modification(PSM),two new composite materials UiO-66-NH2@PMAA and HMS@?-CD@PPP were designed and prepared,and were further used as enzyme carrier and controlled drug release systerm,respectively.The specific research contents of this paper are as follows:(1)The synthesis of UiO-66-NH2@PMAA composite material and its application for pectinase immobilizationThrough a combination of ATRP,Click chemistry and PSM,a hybrid polymer-MOFs architecture UiO-66-NH2@PMAA was synthesized by tethering polymethacrylic acid(PMAA)onto the surface of the Zr-based material UiO-66-NH2.In addition,PXRD,FTIR and IH NMR demonstrated that the crystalline structure of the UiO-66-NH2 framework didn't change after PSM.The result of BET surface areas for UiO-66-NH2 was 1052 m2/g,which suggested that UiO-66-NH2 was of large surface area as the host support matrix.The morphologies of the samples by Tranmitance electric micrography(TEM)and Scanning electric micrography(SEM)were uniform and neat,the mean size of the particles was nearly 180?200 nm.UiO-66-NH2@PMAA was further used as pectinase carrier.Polymethacrylic acid(PMAA)was selected to provide sufficient binding sites(carboxyl groups)for immobilizing pectinase via simple electrostatic adsorption.The optimal immobilization parameters were at 25 ? and pH 4.0 with 10 U/mL of pectinase for 2 h,under which pectinase showed the highest enzymatic activity(1.215 U/mg)and protein loading(448.5 mg/g),respectively.Compared with free pectinase,the immobilized was found to exhibit higher pH,thermo and storage stability.Additionally,the immobilized pectinase had remarkable reusability,the residual activity reached as high as 81%after 8 cycles continuously.Meanwhile,desorption of immobilized pectinase can be achieved by changing pH values of the medium,which was help to achieve the separation and recycling of enzyme.(2)Study on preparation and controlled drug release property of hollow mesoporous silica nanoparticles/dual responsive polymers composite materialpH and light dual-sensitive composite material was prepared for the co-delivery and controlled release of paclitaxel(PTX)and cisplatin(CDDP).First,HMS nanoparticles were synthesized with the use of cetyltrimethylammonium bromide(CTAB)and polystyrene(PS)hollow spheres as dual templates.Then,it was modified by(3-cyclodextrin(?-CD)to obtain HMS@?-CD.Meanwhile,the polymers contained azobenzene groups PPEGMA-PPMA-PMAAMA(PPP)was prepared through the methods of ATRP and Click chemistry.Finally,HMS@?-CD and PPP were self-assembled through host-guest chemistry to achieve pH and light dual-sensitive HMS@?-CD@PPP composite material.1H NMR and FTIR confirmed the structures were accurate;the results of GPC indicated that the polymers were well controlled with low polydispersities.Dynamic Light Scattering(DLS)indicated that the composite material exhibit unimodal size distribution and the sizes reduced with the increase of pH values.The results of TEM demonstrated that composite microspheres were of hollow structure,uniform size and neat morphology.PTX and CDDP were used as model drugs.Two single drug-loaded systems PTX@HMS@?-CD,HMS@?-CD@PPP@CDDP and a dual drug co-delivery system were prepared.PTX was first loaded in channels of mesopores of HMS via physical adsorption before the self-assemble of HMS@?-CD,PTX@HMS@P-CD and PPP,while Pt(II)was conjugated with carboxyl groups to form pH-responsive crosslinking network to obtain the dual drug co-delivery system.The drug-loading efficiency and encapsulation efficiency of PTX and CDDP were 6.20%,33.1%and 13.7%,79.4%,respectively.This carrier could release PTX and CDDP in a control manner under UV-irradiation and acidic conditions.The results showed that the HMS@?-CD@PPP composite material had obvious pH and light responsiveness in vitro.MTT method was used to measure inhibition rate of A549 cancer cells,even at the concentration of HMS@?-CD@PPP up to 400 ?g/mL,the cell viability was 84%.Results of MTT showed that the composite material had low cytotoxicity and good biocompatibility.Furthermore,in contrast with free single drug or single drug-loaded nanoparticles,HMS@?-CD@PPP complex exhibited higher cytotoxicity towords A549 cells.All the data showed that PTX and CDDP have synergistic effect.