| Cancer is the leading cause of death worldwide.Gold nanostructure-mediated photothermal therapy is a promising candidate for cancer treatment.By complexing gold structures with photosensitizers,photothermal therapy can be coordinated with photodynamic therapy to improve anti-cancer efficacy.In this dissertation we report two strategies to achieve this goal.We designed chlorin e6-funcationalized gold nanostars(GNS-PEG-Ce6)to allow coordinated photodynamic/photothermal therapy upon single laser irradiation based on the different photostabilities between photosensitizers and gold nanostructures.The cellular uptake of GNS-PEG-Ce6 was recorded by fluorescence imaging and flow cytometry.The synergistic effect of coordinated photodynamic/photothermal therapy was confirmed in lung cancer and breast cancer cell lines in vitro.The in vivo therapeutic process was monitored by photoacoustic,fluorescence and thermal imaging.Upon single laser irradiation,the GNS-PEG-Ce6 showed significantly higher anti-cancer efficiency than either gold nanostars or chlorine e6 alone both in vitro and in vivo.We also developed a multifunctiotial theranostic platform based on photosensitizer-loaded plasmonic vesicular assemblies of gold nanoparticles(GNPs)for effective cancer imaging and treatment.The gold vesicles(GVs)composed of a monolayer of assembled GNPs show strong absorbance in the near-infrared(NIR)range of 650-800 nm,as a result of the plasmonic coupling effect between neighboring GNPs in the vesicular membranes.The strong NIR absorption and the capability of encapsulating photosensitizer Ce6 in gold vesicles(GVs)enable tri-modality NIR fluorescence/thermal/photoacoustic imaging-guided synergistic photothermal/photodynamic therapy(PTT/PDT)with improved efficacy.The Ce6-loaded GVs(GV-Ce6)have the following features:i)high Ce6 loading efficiency due to the hollow interior of the GVs;ii)enhanced cellular uptake efficiency of Ce6;iii)simultaneous tri-modality NIR fluorescence/thermal/photoacoustic imaging;iv)synergistic PTT/PDT treatment with improved efficacy using single wavelength continuous wave laser irradiation.In addition,the multifunctional vesicular nanocarrier has high solubility and stability in water,non-cytotoxicity,and good biocompatibility,thus facilitating its biomedical applications,particularly as cancer theranostics. |
