Theranostic,Peroxidase-like Activity,and Biosafety of Functional Nanomaterials

Author:Yu Jie

Supervisor:ma xiao yan


Degree Year:2018





Functionalized nanomaterials that can absorb near-infrared(NIR)light to generate heat or convert it to visible light have gained much attention,because the NIR light deeply penetrates organisms and negligibly damages normal tissue.Among them,molybdenum disulfide(MoS2)nanomaterials and lanthanide-doped sodium yttrium fluoride(NaYF4:Yb,Er)nanoparticles have been investigated in varies fields such as cancer theranostic,energy conversion and storage,and catalytic,due to their large specific surface area,manipulated surface,and unique properties.However,more efforts were needed to explore the new applications of these nanomaterials,and the investigations about their biosafety are still in their infancy.In this thesis,multifunctional MoS2 nanomaterials and NaYF4:Yb,Er nanoparticles were synthesized by hydrothermal method.The issues about these nanomaterials were studied:(1)a theranostic nanocomposite consisted of MoS2 nanomaterials and other multifunction components was developed for cancer diagnosis and therapy;(2)a new sensing platform aimed at medical diagnosis was established based on the peroxidase-like activity of MoS2 nanomaterials,and their peroxidase-like catalytic mechanism was investigated by steady-state kinetic assay;(3)the biosafety of MoS2 and NaYF4:Yb,Er nanomaterials was investigated,and diverse behaviors in biodistribution and excretion for NaYF4:Yb,Er nanoparticles were studied by different administration route.First,the MoS2/Fe3O4 composites(MSIOs)functionalized by biocompatible polyethylene glycol(PEG)were prepared by a simple two-step hydrothermal method.MSIOs exhibited high stability in bio-fluids and low toxicity in vitro and in vivo.It can be applied as a dual-modal probe for T2-weighted magnetic resonance(MR)and photoacoustic tomography(PAT)imaging due to their superparamagnetic property and strong NIR absorption.An effective result for magnetically targeted photothermal ablation of cancer was also obtained by using MSIOs.All results show a great potential for localized photothermal ablation of cancer spatially/timely guided by the magnetic field and indicated the promise of the multifunctional MSIOs for applications in cancer theranostics.Second,polyvinylpyrrolidone modified MoS2 quantum dot(PVP-MoS2 QDs)in high purity and yield were prepared by a facile one-pot hydrothermal method.Cytotoxicity and hemolysis studies demonstrated that PVP-MoS2 QDs show good biocompatibility.It exhibited remarkable peroxidase-like catalytic activity,which was similar to that of horseradish peroxidase(HRP).A platform for colorimetric detection of H2O2 was established based on this peroxidase-like activity.Furthermore,the PVP-MoS2 QDs were also used for glucose measurement in serum by quantifying the released H2O2 in the presence of glucose oxidase.This work will pave a way for the high-throughput synthesis of other ultra-small transition metal dichalcogenide(TMDs)QDs,and it could be a useful tool for medical diagnosis.Third,MoS2 nanoflakes(MoS2 NFs)with diameter of 400 nm in high purity were obtained by a facile one-pot hydrothermal method.After modified by polyethyleneimine(PEI),polyacrylic acid(PAA),polyvinylpyrrolidone(PVP),and cysteine(Cys),the peroxidase-like activity of different modified MoS2 NFs was investigated by using3,3’,5,5’-tetramethylbenzidine(TMB)and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)diammonium salt(ABTS)as chromogenic substrates.Compared with polymer modified MoS2 NFs,raw MoS2 NFs and Cys-MoS2 NFs exhibited high catalytic activity toward H2O2in the presence of TMB,but only cysteine-MoS2 NFs have a high catalytic activity toward H2O2 in the presence of ABTS.δ-potential test and Michaelis-Menten analysis implied the surface charge of MoS2 NFs plays a key role in the catalytic reactions when TMB as substrate.However,a transient state of Cys-MoS2 NFs containing H2O2 and ABTS was formed,and the catalytic reaction could proceed because of the cysteine on the surface of MoS2 NFs,which served as the electron transfer bridge between H2O2 and ABTS.Based on these findings,we compared the different capabilities for detection of H2O2 based on MoS2 NFs and cysteine-MoS2 NF.The detection limit was determined to be 4.103μM for H2O2 detection and linear range was from 0 to 0.3 mM.Further,a platform for colorimetric detection of glucose was established using Cys-MoS2 NFs as peroxidase substitution.The detection limit for glucose detection was 4.103μM and the linear range was from 0.05 to 1 mM,which was suitable for biomedical diagnosis.This work provides a new insight into the mechanism of peroxidase-like activity of MoS2 nanomaterials,and paves a way for the nanomaterials with enzyme-like activity to be used for medical diagnosis.Finally,PEI modified NaYF4:Yb,Er upconversion nanoparticles(PEI@UCNPs)were synthesized by one step solvothermal method.The biodistribution of PEI@UCNPs in mice was studied by different administration route,including intravenous(i.v.),intraperitoneal(i.p.),and intragastric(i.g.)administration.64Cu labeled PEI@UCNPs were i.v.injected for real-time photon emission computed tomography(PET)imaging to further confirm the biodistribution in mice,and the excretion routes of the PEI@UCNPs were also evaluated.Hematology,body weight,and biochemical analysis were used to further quantify the potential toxicity of the UCNPs.This dissertation focused on the development of NIR photothermal and upconversion nanomaterials for cancer theranostic,peroxidase-like catalysis,and biosafety,and it paves a way for the design and application of multifunctional nanomaterials in biomedical and catalytic sensing area.