Molybdenum Disulfide-based Nanocomposites For Targeted Photothermal Therapy Of Tumor And Bacterial Infection

During the last few decades,nanoscience and nanotechnology have achieved great progress,and numerous nanomaterials have emerged with unique properties for nanomedical applications.Novel inorganic two-dimensional transition metal dichalcogenides nanosheets?2D TMDC NSs?,such as MoS₂ NSs,WS₂ NSs,MoSe₂ NSs,WSe₂ NSs,etc.,exhibit unique structure and properties,and have been applied for biosensing,bioimaging,drug delivery,photothermal therapy?PTT?,antibacteria,and so on.As a typical 2D TMDC nanomaterial,MoS₂ NSs possess large specific surface area,excellent photothermal property,and good biocompatibility,showing great potential for biomedical applications.Here,the antimicrobial ability of MoS₂ NSs was studied,and MoS₂ NSs-based theranostic agent for cancer and targeting PTT agent for bacterial infection have been prepared by surface modification and bimolecular functionalization.Meanwhile,corresponding application have been achieved both in vitro and in vivo.These results have demonstrated that MoS₂ NSs are not only excellent PTT agent but also promising nanoplatform of multifunctional nanocomposites for biomedical applications.This thesis was described in three parts.1.RGD-QD-MoS₂ nanosheets for targeted fluorescent imaging and photothermal therapy of cancerThe fast-developing field of nanotechnology provides unprecedented opportunities for the increasing demands of biomedicine,especially for cancer diagnostics and treatment.Nanocomposites that combine diagnostic and treatment functions have been studied widely for theranostic applications of cancer.Here,novel multifunctional zero-dimensional-two-dimensional?0D-2D?RGD-QD-MoS₂NSs with excellent fluorescence,photothermal effect,and cancer-targeting properties were successfully prepared by functionalizing single-layer MoS₂ NSs with fluorescent quantum dots?QDs?and arginine-glycine-aspartic?RGD?containing peptides.By using RGD-QD-MoS₂ NSs as a multifunctional theranostic agent,targeted fluorescent imaging of human cervical carcinoma?HeLa?cells were achieved,and over 85%HeLa cells were killed under irradiation of 785 nm laser at the power density of 0.4 W/cm².Moreover,HeLa tumors in mouse models can be fluorescently imaged and completely eradicated by photothermal irradiation using a low power NIR laser?0.8 W/cm²?,due to the effective accumulation of RGD-QD-MoS₂ NSs at the tumor sites through the RGD-integrin interaction and the enhanced penetration and retention?EPR?effect.Without exhibiting any appreciable toxicity to cells or animals,RGD-QD-MoS₂ NSs have been demonstrated as promising multifunctional theranostic agents for cancer imaging and therapy.2.Antimicrobial ability of MoS₂ nanosheetsThe emerging of antibiotic-resistance have terminated the Golden Age of antibiotics started by penicillin,and alternative strategy is in great demand.Nanomaterials have shown unique antibacterial abilities.Here,the antimicrobial property of single-layer MoS₂ NSs was studied.MoS₂ NSs at a very low concentration?8?g/mL?showed an inactivation efficiency of over 80%to Escherichia coli and98%to Staphylococcus aureus,respectively.In nutrient medium,the growth and biofilm formation of bacteria was inhibited by over 75%.The antifungal ability of MoS₂ NSs was a little weaker with an inactivation rate of 60%to Candida albicans,whose biofilm formation was inhibited by 50%.However,the growth of C.albicans in YPD medium was not affected by MoS₂ NSs.Surface modification and functionalization could improve the antimicrobial ability and photothermal ablation efficiency of MoS₂ NSs for the treatment of microbial infection,which would attract great attention.3.Targeted photothermal therapy of S.aureus focal infection based on antibody-functionalized MoS₂ nanosheetsBacterial infectious diseases are placing significant burden on healthcare systems due to the resistance to both antibacterial agents and host immune system provided by biofilms,which account for most of the bacterial infections.Targeted photothermal therapy shows great potential for the treatment of bacterial infections with improved therapy efficacy and reduced side effects.Here,a S.aureus targeting PTT agent based on polydopamine?PDA?coated MoS₂ NSs and anti-protein A IgG was prepared with high integrating stability,great colloidal stability,and good biocompability.The obtained MoS₂@PDA-PEG/IgG?MPPI NSs?showed excellent targeted photothermal ablation ability of S.aureus biofilms with a more than 4 log?>99.99%?inactivation in vitro,while the MoS₂@PDA-PEG NSs?MPP NSs?without targeting moiety can only achieve an inactivation ratio of 90%.Moreover,after the in-situ injection of MPPI NSs at a very low dose of 4?g and NIR laser irradiation at a low power density of 0.58 W/cm²,the S.aureus infected skin of mouse models showed almost healed morphology with only a little bit granulomatous inflammation left at the eighth day after treatment.On the contrary,severe inflammatory response were still observed from the MPP NSs plus NIR laser treatment group.These results demonstrate that targeting moiety significantly improves the treatment efficacy of PTT.Moreover,with great biocompatibility both in vitro and in vivo,the MPPI NSs have been demonstrated as a promising photothermal agent for the treatment of biofilm infections.