Application Of W₁₈O₄₉ Nanospheres On Cancer Photothermal Therapy

Cancer is one of the dominant causes of death in the worldwide and thus it is a great challenge to the public health.Conventional cancer therapies suffer from some unavoidable disadvantages and limitations,hence,it extremely needs to develop new methods for the cancer treatment.Photothermal therapy is an emerging method for cancer remedy proposed in recent years.Under the irradiation of near-infrared(NIR)laser which is set outside the body,the photothermal agents inside the tumor can absorb the NIR light and convert the light energy into heat,so that the temperature at the tumor site rapidly increases over 48 oC,resulting in cancer cell death within minutes.Photothermal therapy has great potential in clinical cancer treatment trials due to the less side-effects,low systemic toxicity and harmlessness to normal tissues.Several types of photothermal agents,including metal nanoparticles,carbon-based nanomaterials,organic nanomaterials and semiconductor nanomaterials,have been fabricated and applied in cancer photothermal therapy with preferable antitumor effect.Nevertheless,development of novel photothermal agents with photoabsorption in the second biological window(1000-1350 nm)and investigation of its application in photothermal cancer therapy remain to be a tough scientific problem.In the thesis,urchin-like tungsten oxide nanospheres with a diameter of approximate 300 nm were synthesized via a solvothermal reaction.The characterization results proved that the nanospheres were of W18O49 crystal phase and possessed strong photoabsorption in the whole NIR region.After irradiation under NIR-1064 nm laser(2.0 W/cm2)for 10 min,the temperature of W18O49 dispersion(0.5 mg/mL)increased by 28.3 oC and massive reactive oxygen species were generated.MTT experiments revealed that the cytotoxicity of W 18O49 nanospheres was very low.Even when W18O49 concentration reached up to 0.5 mg/mL,the cell viability of HeLa cells remained to be higher than 85%.NIR-1064 nm irradiation(2.0 W/cm2)on the W18O49 nanospheres enriched He La cells resulted in severe cell necrosis and apoptosis,and the area of dead cells enlarged to the prolongation of the irradiation time.Apoptosis of He La cells was confirmed to be a result of mitochondrial apoptotic pathway triggered by W18O49 nanospheres-generated heat and reactive oxygen species.In vivo photothermal treatment on He La tumor-bearing mice determined that W18O49 nanospheres-mediated photothermal therapy had excellent tumor inhibitory effect,meanwhile,no adverse effects on mice growth was observed and the structure of the main organs in mice(heart,liver,spleen,lung,kidney)remained to be normal.Further study showed that W18O49 nanospheres did not produce significant toxicity to the mice blood in the long-period circulation process,and in vivo metabolism of W18O49 nanospheres was mainly performed by the liver and spleen.Photoacoustic imaging proved W18O49 nanospheres as an excellent photoacoustic imaging agent because tumor could be well distinguished from other tissues in mice by photoacoustic imaging after intratumoral injection of W18O49 nanospheres.W18O49 nanospheres enriched at tumor site at 12 h post tail intravenous injection due to passive tumor targeting ability.Taken together,urchin-like W18O49 nanospheres were synthesized and successfully applied in photoacoustic imaging guided photothermal therapy.The research in this thesis provided other nanomaterials for photothermal therapy and broadened the wavelength range of incident light for photothermal therapy of cancer,as well as provided new thoughts for cancer diagnosis and treatment.