Synthesis Of Mixed Valence Tungsten Oxide-based Nanomaterial For The Application Of Photothermal Therapy

Recently, photothermal therapy (PTT), which uses photoabsorbing agents forlocalized heating tumor under near-infrared light irradiation, is receiving increasedattentions as a promising treatment alternative to conventional approaches for achievingthe specific elimination of tumor with minimal invasion and high selectivity since itstherapeutic effect happens only at the tumor site where both light-absorbent andlocalized laser radiation coexist. Effective implementation of PTT is inseparable fromthe long wavelength near-infrared (NIR) laser and PTT agents with promoted absorptionat the site coincided with wavelength of NIR laser. Although many kinds ofnanomaterials with plasmon resonance are currently used as PTT agents, synthesiticmethod for these nanomaterials is too complexed and hard to realize morphology-controllable synthesis. In addition, in terms of NIR absorptive properties, they haveseveral unavoidable shortcomings such as narrow absorption spectrum, weakabsorptivity and light stability, as well as irresponsive to the second NIR windowbetween1000and1400nm where has been proven to possess deeper tissue penetrationability. Therefore, it is highly desirable to develop new NIR light nanoabsorbents withstrong absorption in the range of1000-1400nm and controllable nanostructures..In this paper, a series tungsten-oxide nanostructures, such as nanospheres,nanowires, columnar nano-brush, spindle nanoparticles and so forth, have been faricatedunder solvothermal condition by employing different combination of tungstenprecursors and organic alcohols, as well as altering molar ratio between them. It hasbeen found that these nanomaterials are of W18O49nature and all show strong opticalabsorption in NIR range from1000to1400nm. Through the comprehensiveconsideration of the morphology and performance of synthesized nanoparticles, thisthesis selected mixed valence tungsten-based nanospheres as the target PTT agent. Toenhance the endocytosis of the nanospheres, the sample was decorated by polylysine(PLL). It has been found that the surface charge of W18O49nanospheres switched from-52.30mV to36.9mV after PPL decoration. The standard MTT assay of nanospheresbefore and after PLL modification indicates good biocompatibility. The opticalmeasurement determined by UV-Vis-NIR spectrometer reveals that nanospheres beforeand after PLL modifed exhibit excellent NIR absorptive properties in the form ofpowder or aqueous dispersion. The intracellular accumulation of nanospheres measuredby ICP-MS examination indicates that tumor cells uptake about6.06wt%feedednanospheres after24h incubation. To test the feasibility of nanospheres as photothermalabsorber, the photothermal conversion test was carried out by irradiating the slurrysolution of nanospheres under1064nm laser. It has shown a rapid and high rise in temperature upon exposure to the laser irradiation even within a short time duration. Forcell experiments in vitro, tumor cells were incubated with PLL modified nanospheresfor24h and then irradiated under1064nm NIR laser at a powder density of1.061W/cm2for10min, the tumor cells can be completely killed. Similarly, for880nm NIRlaser, power density of2.122W/cm2together with6min irradiation can completelydamage tumor cells.The results of this thesis show that we have developed mixed valence W18O49nanoparticles with excellent NIR absorbing ability in an easy and morphologicalcontrolled way. The PTA study employing1064nm laser in the second NIR windowrevealed that W18O49nanospheres could produce obviously hyperthermia effect insidecancer cells and induce significant cell necrosis and apoptosis.