Preparation,Characterization,Photothermal Effect And Tumor Cell Imaging Of Copper Sulphide Nanocomposites

As a promising alternative or supplement to conventional cancer treating approaches,photothermal therapy?PTT?has great potential for future clinical treatment of breast cancer because of its advantages including controllable treatment process,high tumor eradication efficiency and small side effects on normal tissue cells.PTT,employing photothermal therapy agents?PTAs?and induced by laser in the near-infrared?NIR,700–1100 nm?region,provides a precise and minimally invasive alternative for cancer treatment.Among many PTAs,copper sulfide?CuS?is a p-type semiconductor nanoparticle and the merits of using copper sulfide NPs in the diagnosis and therapy of disease are not only the low cost and toxicity,but also the intrinsic strong NIR absorption,rendering a promising alternative for photothermal ablation of cancerous cell.However,insufficient visualisation towards the drug delivery,distribution,metabolism and digestion of PTT agents,as well as the limited tissue penetration ability of visible or NIR light,seriously restricts the in-depth application of PTT.Therefore,developing breast cancer cells targeted CuS composite nanoparticles for imaging-guided enhanced PTAs is meaningful.In this thesis,the application of NIR responsive nanomaterials for tumor imaging and PTT synergistic treatment were reviewed.Three different CuS nanocomposites were designed and synthesized.The nanostructures were characterized and determined by UV,IR,TEM and AAS.The performance of photothermal conversion,bioimaging?fluorescence imaging and MRI?and drug release in vitro have also been studied.The main novelty is as follows:?1?A breast cancer sensitive nanoparticle PDAMn-CuS@BSA-FA?NPs?was constructed by the electronic state interaction,coordination and hydrophobic interaction based on the layer by layer assembly strategy.The NPs/water system shows the reversible temperature change under the NIR light irradiation with the photothermal conversion efficiency of 66.0%.The photoinitiated cytotoxicity indicates that NPs can be employed as effective NIR light initiated photothermal attenuators.In particular,the emission of the nanoparticle at 520 nm increased with the titration of CH₃O-PEG-phosphatide.Moreover,MCF-7 cells lysis switched on the green emission of NPs greatly,in contrast,weak emission can be found in normal cells lysis.It indicates that PDAMn-CuS@BSA-FA can be a breast cancer activated nanosensor.And also,MCF-7 cell turn-on fluorescence image and selective T₁ MR Image demonstrate the NPs can enter MCF-7 cells.Our results provide a convenient method for the development of non-aptamer cancer activated nanoprobes or drug carriers based on the CH₃O-PEG-phosphatide recognized nanoparticles.This has been the first reported nano-fluorescent probe activated by breast cancer cell used as multifunctional PTA for the recognition and diagnosis of breast cancer.?2?A novel gadolinium doped copper sulfide nanoparticles?GdCuS?with better photothermal efficiency?46%?under the NIR light irradiation were synthesized.It can be used in dual-mode imaging and photothermal treatment reagent for breast cancer cells.Furthermore,GdCuS-DMP nanoparticles with NIR light have a higher inhibition rate for breast cancer cells.The fluorescence of GdCuS-DMP can be turned on by bovine serum albumin?BSA?and MCF-7 cells.Meanwhile,MCF-7 cell imaging confirmed the targeted performance of the nanoparticles in breast cancer,which further indicated GdCuS-DMP nanoparticles can be PTAs for breast cancer.Besides,GdCuS-DMP nanoparticles synthesized by one step also has T₁ magnetic resonance signal which has been proved in vitro MR imaging of MCF-7 cells.Hence,GdCuS-DMP prepared for the first time with low toxicity,breast cancer targeting and biocompatibility can be dual-mode?fluorescence and MR?imaging-guided PTAs for breast cancer.?3?The nucleic acid-fluorescence copper sulfide-silicon nanoparticles?CuS@mSiO₂-RPM@PTX?were prepared,and the results showed that Rhodamine B isothiocyanate?RhBITC?combined with CuS had a good photothermal conversion efficiency?53%?under irradiation of 808 nm NIR light.The modification of nucleic acid?MUC1?increased biocompatibility and tumor cell absorption of nanoparticles.And also,red fluorescent imaging of MCF-7 cells indicates that nanoparticles can enter cells.Additionally,nanoparticles have the release of the drug?PTX?with pH and NIR light response,and also have the effect of slow-release later.In addition,effective inhibition of MCF-7 cells induced by thermal and drug of PTX activated by NIR light has also been proved in MTT test.Therefore,the new type of CuS-mSiO₂-RPM@PTX can be theranostic nanoparticle for fluorescence imaging-guided PTT and chemical therapy,which provide a new platform for the diagnosis and treatment of breast cancer.