Controlled Synthesis And Surface Functionalization Of Nanomaterials For Tumor Theranostic Applications

The development of efficient methods for the controlled synthesis of nanocrystalswith monodispersity, stability, and predictable morphology is one of the key goals in theadvancement of nanoscience and nanotechnology. Afterwards, the surfacefunctionalization of nanomaterials promotes the extensive applications of nanotechnologyin biomedical field. In the burgeoning nano-bio-medicine field, use of advancednanomaterials and smart stimuli-responsive nanostructures for the diagnosis and treatmentof disease can provide the direct evidence to early diagnosis, occurrence and developmentprogresses of disease, and also enables online imaging of drug for the detection of disease,image-guided drug delivery and treatments, guidance of surgical resection, and monitoringof treatment response.This dissertation mainly includes （1） two kinds of controlled synthesis methods ofnanomaterials and their mechanism investigation.（2） surface functionalization ofnanomaterials for tumor theranostic applications. The main contributions are as follows:1. Controlled synthesis of metallic and upconversion rare earth fluoride nanocrystals vialiquid-liquid two-phase system.（1） Monodisperse metallic nanocrystals with a narrow sizedistribution such as Ag, Cu, Ni and Fe nanoparticles were synthesized in the toluene-watertwo-phase system at room temperature. A possible mechanism for the formation ofmonodisperse nanocrystals is also discussed.（2） Highly uniform and monodisperse REF₃and NaREF₄（RE=La, Gd, Yb and Y） nanocrystals with small size （<25nm） anddifferent morphologies were synthesized in the oleic acid （OA）/ionic liquids （ILs）two-phase system. A possible mechanism for the formation of monodisperse nanocrystalsis also discussed.2. Bovine serum albumin （BSA）-conjugated MxSey（M=Ag, Cd, Pb, Cu） nanomaterialswith different shapes and sizes were synthesized in water at room temperature by aprotein-directed, solution-phase, green synthetic method. A possible mechanism for theformation of semiconductor chalcogenides in the BSA solution is discussed. 3. Design and preparation of photosensitizer-conjugated magnetic nanoparticles. Thisnanoprobe can offer magnetically guided drug delivery under external magnetic field,induce hyperthermia under an alternating magnetic field, and display remarkablephotodynamic efficacy upon laser irradiation. Our results indicated that the synthesizedmultifunctional nanoprobe is potential for magnetically guided drug delivery,simultaneous magnetofluorescent imaging-guided dual-modal photodynamic therapy（PDT） and hyperthermia.4. Design and preparation of folic acid-conjugated silica-modified gold nanorods. Thisnanoprobe show highly selective targeting, enhanced radiation therapy （RT） andphoto-thermal therapy （PTT） effects on MGC803gastric cancer cells, and also exhibitedstrong X-ray attenuation for in vivo X-ray and computed tomography （CT） imaging. Thesynthesized nanoprobe is a good candidate with excellent imaging and targeting ability forX-ray/CT imaging-guided targeting dual-modal enhanced RT and PTT.5. Design and preparation of folic acid-conjugated graphene oxide （GO）. Thephotosensitizer （PS） Chlorin e6（Ce6） was effectively loaded into the system viahydrophobic interactions and π-π stacking. The nanocarriers can significantly increase theaccumulation of Ce6in tumor cells and lead to a remarkable photodynamic efficacy onMGC803cells upon irradiation. These suggested that folic acid-conjugated GO loadedCe6had great potential as effective drug delivery system in targeting PDT.6. Design and preparation of chlorin e6-conjugated C-dots （C-dots-Ce6）. C-dots canenhance the fluorescence of Ce6on C-dots-Ce6by the F rster （fluorescence） resonanceenergy transfer （FRET）. The C-dots-Ce6owns good stability, noncytotoxicity, goodbiocompatibility, enhanced photosensitizer fluorescence detection and remarkablephotodynamic efficacy upon irradiation. The synthesized nanoprobe is effective forsimultaneous enhanced-fluorescence imaging-guided PDT.