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

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.?-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 4.103?M 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 4.103?M 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.