Near-Infrared Light-Mediated Nanotherapeutic Systems For Cancer Phototherapy And Imaging

As a representative innovation in cancer therapy,theranostic nanoparticles,which integrate multiple imaging modalities and therapeutic functionalities,have been extensively exploited for simultaneous cancer diagnosis,therapy,and monitoring the therapeutic efficacy.Among these nanostructures,therapeutic agents that are responsive to external physical stimuli,especially near-infrared light,have received substantial attention attributed to their non-invasiveness,safety and remote-controllable properties.The present work focuse on the fabrication of near-infrared light-mediated nanoplatforms for multimodal imaging-guided photothermal and photodymic therapy.Chapter 1 introduces the basic concepts of near-infrared light-triggered phototherapy,imaging technigues,and nanomaterials that are commonly employed as phototherapeutic and contrast agents.Thereafter a brief description of theranostic,including its development and representative theranostic nanoparticles,is presented.In Chapter 2,a novel phototherapy nanoplatform is prepared by coating hollow CuS nanoparticles with a bovine serum albumin-folic acid(BSA-FA)complex.The obtained CuS-BSA-FA nanoparticles are used as drug-delivery vehicles to transport a near-infrared-absorbing phototherapeutic agent(indocyanine green,ICG)into HeLa cells,after loading ICG onto CuS-BSA-FA.In this manner,a combined therapeutic approach is established consisting of photothermal therapy,by CuS-BSA-FA nanocarriers,and cytotoxic effect of photodynamic and photothermal therapy,by ICG upon 808 nm laser irradiation.The encapsulation of ICG onto CuS-BSA-FA significantly improves the stability and reduces the dark toxicity of free ICG This therapeutic system exhibits obvious higher photothermal heating effect and capability of singlet oxygen(1O2)generation under laser irradiation compared with bare nanocarriers.In addition,the grafted FA segments on the surface of CuS-BSA-FA are proved to enhance the internalization of nanoparticles by the FA-receptor-mediated endocytosis.In Chapter 3,a protein-stabilized multifunctional theranostic nanoplatform,gadolinium oxide-gold nanoclusters hybrid,shortly termed as Gd2O3-AuNCs,is constructed for multimodal imaging and drug delivery.The Gd2O3-AuNCs nanohybrid is developed by integrating Gd2O3 nanocrystals and gold nanoclusters into bovine serum albumin scaffold as a stabilizer.The nanohybrid exhibits favorable biocompatibility and is capable of enhancing the contrast in magnetic resonance(MRI)and X-ray computed tomography(CT)imaging.Meanwhile,the integrated AuNCs component not only endows the nanohybrid to produce red fluorescence,but also sensitizes the generation of 1O2 upon near-infrared laser stimulation at 808 nm.Bovine serum albumin surrounding the nanoparticles makes Gd2O3-AuNCs a brilliant carrier for the delivery of indocyanine green.ICG loading endows the Gd2O3-AuNCs-ICG nanocomposite with a near-infrared fluorescence(NIRF)imaging capability,and improves its photodynamic property and photothermal capability.In vitro phototherapy and in vivo NIRF/MRI/CT imaging experiments have demonstrated that Gd2O3-AuNCs-ICG nanocomposite is a promising theranostic agent for image guided cancer therapy.In Chapter 4,a magnetic therapeutic platform containing dual photothermal agents,polypyrrole(PPy)and gold nanoshell,is constructed for the purpose of improving the diagnosis and enhancing the photothermal therapeutic effect under near-infrared(NIR)laser irradiation.The nanostructure is composed of a magnetic PPy/Fe3O4-core and a gold nanoshell,which is capable of enhancing the contrast for both magnetic resonance and X-ray computed tomography imaging.By attaching Raman probes onto the surface of gold shell,the nanocomposites exhibit the potential to serve as surface-enhanced Raman scattering(SERS)active substrates for optical modality identification of cancer cell.The capability of the therapeutic nanoplatform as photothermal agent is further demonstrated by effective ablation of cancer cells upon exposure to NIR laser at 808 nm,which is highly promising for multimodal imaging-guided cancer treatment.