Bimetallic Chalcogenide Based Theranostic Nanoprobes

Background: For centuries,cancer has been one of the major causes of death and seriously threatens human beings' health.Therefore,precise diagnosis and treatment of cancer at an early stage is an important stategy to reduce its high mortality.The clinically used imagingtechniques for cancer diagnosis mainly include magnetic resonance imaging(MRI),computed tomography(CT),and ultrasound imaging.However,the individual imaging technique has its own advantages and disadvantages in terms of sensitivity and resolution.In this context,complementary multimodal imaging has great potential in early and accurate diagnosis of cancer.The main methods of cancer treatment are surgery,chemotherapy and radiotherapy.However,in many cases,surgery can not completely remove all the cancer cells in the body.Both chemotherapy and radiotherapy have limited specificity and selectivity to cancer cells,and have serious side effects on normal tissues.Compared with conventional treatment methods,photothermal therapy,especially the therapy with near-infrared(NIR)light has attracted considerable attention,because it can selectively kill cancer cells with less toxic photothermal transducer agents,and without too much damage to normal tissues.In addition,the transducers of photothermal therapy can be also used for photoacoustic imaging,which makes the feasibility of simultaneous diagnosis and treatment with the same agent on the same instrument.Many researchers have demonstrated that ternary bimetallic chalcogenides with excellent physicochemical properties have unique advantages and potential in the nanobiomedical field,such as in vivo multimodal imaging,tumor photothermal therapy and antitumor drug delivery.In this thesis,Cu-Fe-Se ternary nanoparticles were prepared by an environment-friendly aqueous method at room temperature.The CuFeSe2 nanocrystals were modified with multifunctional PTMP-PMAA polymer to show excellent water solubility,colloid stability,biocompatibility and versatility.The narrower band gap and a middle valence band formed by Fe3+ doping lead to broad intense absorbance in the near infrared region.The presence of magnetic Fe3+ and small nanosize effects of CuFeSe2 nanocrystals also results in their superparamagnetism.The relatively higher effective atomic number and X-ray attenuation coefficient make them promising for CT imaging.These unique properties make them as an ideal theranostic agent for multimodal imaging,such as photoacoustic(PA)imaging,MRI,and CT imaging,to guide photothermal therapy of cancer.Objective: The aim of thesis is to achieve accurate diagnosis and treatment of breast cancer through multimodal imaging guided photothermal therapy by using bimetallic chalcogenide nanoparticles as theranostic agent.Methods: In this thesis,multimodal imaging and multimodal therapy of breast cancer are mainly performed by using bimetallic chalcogenide nanomaterials.Firstly,ultrasmall CuFeSe2 nanoparticles were prepared by an ambient aqueous method,and characterized with state-of-art facilities to reveal their structure and properties.Secondly,the biocompatibility of CuFeSe2 nanocrystals was assessed by cytotoxicity test and blood routine biochemical experiments.After that,in vitro imaging and photothermal performance of CuFeSe2 nanocrystals would be tested.Finally,the in vivo application of CuFeSe2 nanocrystals in multimodal imaging guided photothermal therapy was tested on a subcutaneous breast cancer model.Results: The CuFeSe2 nanoprobe not only serve as a PA and CT contrast agent,but also as a SPECT agent after labeled with radionuclide(Technetium,99mTc),which can achieve the accurate diagnosis of breast cancer with complementary multimodal imaging.Meanwhile,CuFeSe2 nanoprobe is used for photothermal therapy of breast cancer monitored with real-time imaging.It can completely kill the tumor cells without the recurrence of tumor.Conclusion:The CuFeSe2 nanoprobe prepared from the simple aqueous method has good biocompatibility,and can be used for SPECT,PA,CT and MR imaging guided photothermal therapy of breast cancer,which could provide a new way for the clinical diagnosis and treatment of breast cancer.Overall,the ultrasmall CuFeSe2 nanoparticles could serve as an ideal theranostic agent with great potential of clinical translation.