The Preparation And Applications Of PVP-Cu-Sb-S Nanoparticles And Bi2S3@MnOx Nanomaterials

Part 1 PVP-Cu-Sb-S nanoparticles for photoacoustic imaging and photothermal/photodynamic therapyObjectivesThis study aims to explore the photoacoustic imaging capability and the photothermal/photodynamic effect of a new PVP-Cu-Sb-S nanoparticle,synthesized by our previous work,in 4T1 breast cancer cells model.It will lay a foundation for nano-scale theranostic agents to achieve early-stage detection and treatment for breast cancer.MethodsFirstly,the mass extinction coefficient,photothermal conversion efficiency and the photoacoustic imaging capability of PVP-Cu-Sb-S nanoparticles were evaluated.Then the heating effect and ROS-generation ability of PVP-Cu-Sb-S nanoparticles under 808nm laser irradiation were also tested.Secondly,the cell viability of 4T1 cells co-incubated with nanoparticles was used to assess the biocompatibility of PVP-Cu-Sb-S nanoparticles,and the photothermal/photodynamic therapeutic effect of PVP-Cu-Sb-S nanoparticles,combined with 808nm laser irradiation,on 4T1 cells was further estimated by fluorescent staining and MTT cytotoxicity assay.Finally,BALB/c tumor bearing mice were used to monitor the photoacoustic imaging capability and photothermal/photodynamic effect in vivo.ResultsThe UV-vis-NIR absorbance spectrum of the as-obtained PVP-Cu-Sb-S nanoparticles showed a wide spectrum extending to the NIR wavelength region(650-900 nm),which represent the NIR response of these nanoparticles.And its mass extinction coefficient and photothermal conversion efficiency was 10.5L g-1 cm-1 and 53.22%,respectively.What’s more,PVP-Cu-Sb-S nanoparticles performed good heating effect,ROS-generation ability and photoacoustic imaging capabilities under 808nm laser irradiation.Next,in vitro cell experiments indicated that PVP-Cu-Sb-S nanoparticles not only possessed lower cell toxicity(the cell viability of 4T1 cells was over 70%at the maximum concentration of PVP-Cu-Sb-S nanoparticles),but also had potent killing effect(photothermal/photodynamic therapy)on 4T1 cancer cells under 808nm laser irradiation.Last but not least,no noticeable tissue disorder was found in the BALB/c mice after intravenous administration of PVP-Cu-Sb-S nanoparticles,and PVP-Cu-Sb-S NPs showed remarkable contrast enhancement according to in vivo photoacoustic imaging.In addition,excellent tumor ablation results could be achieved by the combination of PVP-Cu-Sb-S NPs and 808 nm NIR laser treatments.ConclusionsThe as-prepared PVP-Cu-Sb-S nanoparticles perform significant photothermal/photodynamic therapeutic effect and photoacoustic imaging capability under 808nm laser irradiation,which shows that they have the potential to be useful targeted nanoagent for the diagnosis and treatment for breast tumor.Part 2 Preparation and applications of Bi2S3@MnOx nanomaterialsObjectivesThe objective of this study is to synthesise bismuth sulfide@manganese oxide nanocomposites with a new structure and explore its tumor microenvironmentactivatable multimodal imaging and combined therapeutic effect in vitro and in vivo using 4T1 breast cancer cells model.MethodsThe properties of bismuth sulfide@manganese oxide nanocomposites were evaluated by obtaining the appearance of nanocomposites in TEM,the biocompatibility in vitro and in vivo,the CT imaging capability and the ability to load and release DOX.In addition,MB degradation experiment and DCFH-DA fluorescent staining were used to verify the nanomaterials-mediated Fenton-like reaction in the presence of GSH.At last,the T1-enhanced magnetic properties of bismuth sulfide@manganese oxide nanocomposites with GSH and the ability of nanocomposites to mitigate tumor hypoxia were also assessed.ResultsThe bismuth sulfide@manganese oxide nanocomposites with a long sausage-shell structure,had good biocompatibility in vitro and in vivo.They could effectively load and release DOX,and perform good CT imaging in vitro.In addition,bismuth sulfide@manganese oxide nanocomposites could consume GSH to catalyze Fenton-like reaction and perform T1-enhanced magnetic properties.For in vitro studies,results showed that bismuth sulfide@manganese oxide nanocomposites could consume GSH and further achieve chemodynamic therapeutic effect in tumor cells,and the bismuth sulfide@manganese oxide nanocomposites-DOX system also could exert chemotherapeutic effects in 4T1 cells.More importantly,these nanocomposites performed good MR imaging capability in vivo,and in vitro and in vivo studies indicated that bismuth sulfide@manganese oxide nanomaterials could react with H2O2 to generate O2 and further mitigate tumor hypoxia status.ConclusionsThe as-synthesized bismuth sulfide@manganese oxide nanocomposites with CT imaging capacity and tumor microenvironment-response T1-enhanced MR imaging capacity can achieve chemotherapy/chemodynamic therapeutic effect in vitro,which indicates that they have the potential to be further researched.