Development Of Small Animal Imaging System And Design Of Functional Nanomaterials Diagnosis And Treatment

In vivo fluorescence imaging of small animals is an important technology in the field of biomedical research.Because of its simple operation,real-time intuitiveness,high sensitivity,and low experimental cost,fluorescence imaging has been widely used in life sciences,medical research,and drug development.Nanomaterials are widely used in biomedicine area to address various medical challenges by traditional medicine,including poor bioavailability,compromised target specificity,systemic and organ toxicity,etc.Nanomaterials have many distinctive advantages,such as versatility,large loading,targeting,and long blood circulation time.Nanomaterials play a key role in biomedicine to efficiently carry and deliver imaging probes,therapeutic agents or biomaterials to target sites such as specific organs,tissues and even cells.In this paper,an imaging system for small animal was designed and two functionalized nanomaterials were synthesized.The nanomaterials were applied for the monitoring MMP-7,diagnosis and treatment of tumor through the developed small animal imaging system.It mainly includes the following three parts:1.A small animal in vivo fluorescence-photothermal dual-mode imaging system is reported,which has dual functions of fluorescence imaging and thermal imaging.The system has high imaging sensitivity,fast acquisition speed,and large tissue penetration depth(up to 10 mm during near infrared fluorescence imaging),and a thermal imaging resolution of 0.1 ℃.The system can not only achieve fluorescence imaging of small animal subcutaneous tumors and deep tissues/organs,but also integrate thermal imaging to real-time monitor temperature changes and the drug release process in photothermal therapy,to achieve precise treatment.2.Peptide-modified MnFe2O4 ratiometric fluorescent nanoprobes were synthesized to monitor the distribution of matrix metalloproteinase-7(MMP-7)in vitro and in vivo.Fluorescein isothiocyanate(FITC)modified peptide(the sequence contains MMP-7-specifically cleaved peptide substrate VPLSLTMG)is combined with MnFe2O4 nanoparticles to construct fluorescence resonance energy transfer(FRET)-based nanoprobes.Another rhodamine B(RhB)-modified peptide can not only be used as an internal reference for relative FTIC fluorescence to construct ratio fluorescence,but the NGR amino acid sequence in it can also be used to enhance tumor molecular targeting ability.In addition,MnFe2O4 nanoparticles have excellent T2-weighted magnetic resonance imaging(MRI)capabilities.In the presence of MMP-7,FITC was detached from the MnFe2O4 surface and the fluorescence signal recovered,while RhB fluorescence did not change significantly.The ratio of FITC to RhB fluorescence intensity was linearly related to the concentration of MMP-7 in buffer or cancer cells.The small animal in vivo imaging system developed in the first part of the work demonstrated that MnFe2O4-pep-dyes can monitor the expression of MMP-7 in mouse tumors through fluorescence imaging signals under the assistance of an external magnetic field.3.Mesoporous silica(mSiO2)coated upconversion luminescent nanoparticles(UCNPs)were prepared,and the surface was loaded with Fe3O4(MNPs),MMP-2 targeting peptide(MTP)and the anticancer drug doxorubicin(DOX).The multifunctional composite nanomaterial was named as UCNP@mSiO2-MNPs/MTP/DOX.Due to the strong upconversion fluorescence of UCNPs,superparamagnetic properties of Fe3O4 nanoparticles,and the porous structure of the mesoporous silica shell,the prepared UCNP@mSiO2-MNPs/MTP/DOX nanomaterials can be used not only as multimodal(UCL/T1/T2)contrast agent,but also as magnetic targeting and molecular targeting anti-tumor drugs by loading doxorubicin(DOX)and MMP-2 targeting peptides.Fe3O4 loaded on mesoporous silica has a certain photothermal conversion performance,resulting in the photothermal therapy ability of the prepared nanomaterials.The small animal in vivo imaging system developed in the first part of the work can be used to monitor the enrichment of nanocomposites at the tumor site,as well as the photothermal therapy and DOX drug release process.