Bi-based Nanomaterials For Cancer Synergistic Thermoradiotherapy

Inorganic nanomaterials attract a great of research interests owing to their unique intrinsic physicochemical properties.We highlighted recent advances in the applications of inorganic nanoparticles of their imaging and therapy efficacy with focusing on tumor imaging nanomaterials including metal-based,carbon-based nanomaterials and quantum dots.Inorganic nanoparticles gain excellent in vivo tumor imaging functions based on their specific characters of strong near-infrared optical absorption and/or X-ray attenuation capability.The specific response signals from these novel nanomaterials can be captured by a series of imaging techniques,i.e.,optical coherence tomography?OCT?,X-ray computed tomography?CT?imaging,two-photon luminescence?TPL?,photoacoustic tomography?PAT?,magnetic resonance imaging?MRI?,surface enhanced Raman scattering?SERS?,positron emission tomography?PET?,and so on.At the same time,such as metal-based nanoparticles,carbon nanotubes-based,graphene-based,C60or C82 based nanomaterials,have been efficient kill cancer cells depend on the photothermal therapeutic or as a radiosensitezer.Functionalization carbon nanotubes and graphene oxide could be as a delivery vehicle to carry drugs by their ultra-high surface area.In this review,we summarized the rapid development of the inorganic nanomaterial bioapplications with using these analysis techniques and discussed the related safety issues of these materials.Based on the concrete direction of our experiment,and we also summarized the Bi-based nanomaterials in biomedical applications.Include synthesis,performance characterization,tumor imaging and therapy and the biological safety evaluation.The main methods,results and conclusions of this dissertation are summarized as follows:To integrate radiotherapy?RT?with NIR light activated photothermal therapy?PTT?is in high require for efficient cancer sherapy.But how to choose which NIR window light has not yst been determined.Here in,we constructed a multifunctional nanotheranostics with amphiphilic nontoxic polymer D-?-Tocopherol Polyethylene Glycol 1000 Succinate?TPGS?-coated bimetallic chalcogenide?Cu₃BiS₃?nanocrystals?NCs?.There CNs could not only convert NIR in the biological I or II window into considerable amounts of localthermal energy for effective thermal ablation based on the strong NIR absorption,but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage in vivo due to the presence of high-Z element Bi.The TPGS-Cu₃BiS₃ exhibited more efficient thermal conversion ability under the irradiation of a 1064 nm laser with a safe power density of 0.5 W/cm².With the synergistic interaction between PTT and the enhanced RT,the 1064 nm laser just need about 1/3 power density and 1/2 irradiation time compare to 808 nm laser,the hepatoma tumors could be eradicated without visible recurrence in 20 days.Moreover,the novel Cu₃BiS₃ NCs facilitate excellent computer tomography?CT?/both NIR I and II window multispectral optoacoustic tomography?MSOT?dual-modal imaging,and provide a potential for RT/PTT synergistic therapy with MSOT/CT bimodal imaging guidance.Our work demonstrates that Cu₃BiS₃ NCs with ideal X-ray absorption property and photohyperthermia performance,could act simultaneously as both the radiosensitizers,photothermal agents and MSOT/CT dual-modal imaging contrast agents,showing significant the synergistic effects on therapy of pancreatic cancer under dual-modal imaging guidance.The development of new generation of nanoscaled radiosensitizer that can not only enhance radio-sensitization of the tumor tissue,but also increase radio-resistance of the healthy tissue is highly desireable,but remains a great challenge.Here,we report a new versitile theranostics based on poly?vinylpyrollidone?and selenocysteine modified Bi₂Se₃ nanoparicles?PVP-Bi₂Se₃@Sec NPs?for simultaneously enhancing radio-therapeutic effects and reducing the side-effect of radiation.The as-prepared nanoparticles exhibit significantly enhanced free radical generation upon X-ray radiation and remarkable photothermal effects under 808 nm NIR laser irradiation,because its strong X-ray attenuation ability and high NIR absorption capability.Moreover,these PVP-Bi₂Se₃@Sec NPs are biodegradable.In vivo,part of selenium can be released from NPs and enter the blood circulation system,which can enhance the immunologic function and reduce the side-effects of radiation in whole body.As a consequence,improved superoxide dismutase?SOD?and glutathione peroxidase?GSH-Px?activities,promoted secretion of cytokines,increased number of white blood cell?WBC?and reduced marrow DNA suppression,were found after radio treatment in vivo.Moreover,there is no significant in vitro and in vivo toxicity of PVP-Bi₂Se₃@Sec NPs during the treatment,which demonstrates that PVP-Bi₂Se₃@Sec NPs have good biocompatilibity.In a word,we designed two kinds Bi-based nanomaterial.We offer a proposal that how to choice the appropriate laser and power density when conbine thermal therapy and radiotherapy for tumor therapy.Then we offer a suggestion that how to resolve the side effect of radiation by nanomaterials from the root of design.At last,we hope that nanomaterials could realize transformation of clinical as soon as possible.