Fabrication Of Two Dimensional Nanotheranostic Systems Towards Cancer Diagnostic And Therapy

Recently,two-dimensional(2D)nanomaterials have drawn considerable attention in the field of drug delivery and cancer theranostic on account of their large specific surface area and abundant surface active sites.As a typical class of 2D nanomaterial,layered double hydroxides(LDHs)consist of edge-sharing MO6 octahedral host layers and negatively-charged interlayer anions.Due to their unique 2D structure with tunability in both host layer and interlayer anions,LDHs have shown potential applications in biomedicine area.In this thesis,LDHs theranostic systems were fabricated by virtue of the versatility in both host layer and charge-balancing anions,leading to a precise control over chemical compositions and functionality regulations.Theoretical studies were carried out on the host-guest interactions to further explore the structure-property correlation,which facilitates the application of LDHs in the fields of cellular imaging and cancer therapy.Moreover,by evaluating the in vivo behaviour and pharmacokinetic performance,the LDHs theranostic system has been demonstrated as a promising candidate towards cancer diagnostic and therapy.The major results of this thesis are shown below:1.Isophthalic acid intercalated LDHs as a two-photon photosensitizer for photodynamic therapyThrough the intercalaton of isophthalic acid(IPA)within LDHs nanosheets,we developed a NIR-activated supramolecular photosensitizers towards highly effective photodynamic therapy(PDT).The 2D confined microenvironment of LDHs promotes the two-photon-induced generation of ultralong-lived triplet exciton with second-scale lifetimes,and thus greatly boosts the 1O2 quantum yields.LDHs-IPA material shows pseudo-hexagonal nanosheets morphology with a controllable diameter distribution and superb stability.With the excitation of two-photon laser,the two-photon absorption(TPA)cross section of LDHs-IPA was measured to be 3000 gm at 860 nm.The excellent 1O2 production of LDHs-IPA was further determined by the characterization of 1,3-diphenylisobenzofuran(DPBF)and electron spin-resonance spectroscopy(ESR),whose 1O2 quantum yield was evaluated as high as 74%.This is much higher than the commercial photosensitizer ZnPc.In vivo tests were used to verify the anti-cancer properties of LDHs-IPA.To study in vivo behavior of LDHs-IPA,a near-infrared(NIR)dye,Cy5.5 was choose to label LDHs-IPA.By taking advantage of the enhanced permeability and retention effect(EPR),LDHs-IPA gives a long blood circulation time of 9.71 h,which facilitates the tumor accumulation of LDHs-IPA.Due to the superior tissue penetration of 808 nm laser irradiation,the as-prepared LDHs-IPA nanosheets material exhibits dramatically strong tumor ablation capabilities and extremely low in vivot oxicity.This work demonstrates a two-photon PDT within a single drug formulation,which can be potentially used in clinical applicatons.2.LDHs monolayer nanosheets towards cancer theranosticLDHs monolayer nanosheets material was designed and prepared via a one-step "bottom-up" method,followed by incorporation with a chemotherapeutic agent doxorubicin(DOX)to obtain DOX/MLDHs drug delivery system.AFM and XRD results show that MLDHs nanosheets possess a thickness of?0.9 nm,corresponding to a single sheet of LDHs matrix.Due to the large specific surface area and abundant surface active sites,the loading capacity of DOX was as high as 3.6 mg mg-1(w/w).In vitro tests performed with KB cancer cells demonstrate a targeting cellular uptake and superior anticancer performance of DOX/MLDHs.In addition,this composite material displays selective release toward cancer cells and good biocompatibility to normal cells,which would guarantee its further applications in cancer therapy.By further exploring the sturcture control over MLDHs,co-doping of Gd3+and Yb3+into LDHs host layer were achieved,giving rise to excellent dual-model imaging functionality.Firstly,AuNCs/Gd-LDHs theranostic material was prepared by immobilizing AuNCs onto the surface of Gd-doped LDHs monolayer nanosheets(Gd-LDHs),which exhibits excellent MR/FL dual-modal imaging performance.In addition,Gd&Yb-LDHs monolayer nanosheets with MR/CT imaging ability were accomplished with an ultrahigh loading of chemotherapeutic drug SN38(LC=925%),which is one order of magnitude enhancement compared with previously reported hydrophobic drug delivery systems.By further introducing ICG(a fluorescence dye),SN38&ICG/Gd&Yb-LDHs material with MR/CT/NIRF tri-mode imaging ability was prepared towards cancer theranostic.Both in vitro and in vivo tests revealed the promising synergetic theranostic performance of SN38&ICG/Gd&Yb-LDHs.