Synthesis Of Functionalized FeS Nanomaterials And Their Applications On Tumor Therapy

Transition metal sulfides（TMCs）have attracted extensive attention in many fields such as energy catalysis,optoelectronics and biomedicines due to their special physicochemicalproperties.Ferrous sulfide not only has many advantages possessed by TMCs including large specific surface area,strong near infrared absorption,low biological toxicity,but also has outstanding magnetic,optical,catalytic properties,etc.,which has been widely applied in antibacteria,biological sensing,biological imaging,tumor therapy and other fields.In recent years,it has become a hot research area in the field of low dimensional functional materials.Herein,FeS ultrasmall nanodots prepared by one-step hydrothermal method were functionalized by constructing heterostructures and nanodrug delivery system to form FeS@Au heterostructures and FeS-melatonin@carboxymethyl chitosan nanomicelles,which were then studied for their application in tumor therapy.The main details of our work are as follows:1.FeS ultrasmall nanodots were firstly prepared by one-step hydrothermal method,and Au thin layers were then extensively grown on the surface of FeS ultrasmall nanodots by reducing chlorauric acid with ascorbic acid（AA）to form FeS@Au heterostructure.The morphology,structure,valence state and lattice spacing of as-prepared FeS@Au heterostructure were characterized.The second near-infrared（NIR-Ⅱ）photothermal and chemodynamic performance,and depletion of glutathione（GSH）of FeS@Au heterostructure were explored.The NIR-Ⅱphotothermal and chemodynamic therapeutic effect was further explored in vitro and vivo.The experimental results show that FeS@Au heterostructure with a good size dispersity and the size of about 5-7 nm has strong absorbance in the NIR-Ⅱregion,and the extinction coefficient at 1270 nm is 24.67 L g^-1 cm^-1.It gives the photothermal conversion efficiency of 35.46%and excellent photothermal stability.The chemodynamic performance of FeS@Au heterostructure is better than that of FeS nanodots,which can efficiently catalyze endogenous H₂O₂ to·OH and the photothermal effect derived from FeS@Au heterostructure can accelerate this catalytic reaction.Notably,external Au layer in FeS@Au heterostructure can efficiently consume GSH,which will efficiently weaken the self-protection mechanism of tumor cells against oxidation,and result in accumulation of a large amount of reactive oxygen species（ROS）.Experiments in vitro and vivo demonstrate that hotothermal effect of FeS@Au heterostructure can amplify tumor oxidative stress and lead to a high ROS level in liver tumor cells,suggesting that FeS@Au heterostructure is a highly efficient multimodal tumor therapy agent with good biocompatibility.2.Ultrasmall FeS nanodots with high specific surface area were used as carrier to realize high loading of melatonin（MLT）.MLT loading FeS nanodots was further coated by the crosslinking reaction of carboxymethyl chitosan（CMC）with glutaraldehyde（GA）to form FeS-MLT@CMC nanomicelles.The morphology、structure,valence state,and surface charge of FeS-MLT@CMC nanomicelles were characterized.The photothermal performance in NIR-Ⅱregion were tested,and the effect of photothermal combined immunotherapy in vitro and vivo was studied.The experimental results show that FeS-MLT@CMC nanomicelles have a spindle shape with the size of 400 nm,and the surface was negatively charged.MLT was successfully loaded on the FeS nanodots with high loading capacity up to 19.08 m M.The absorbance of FeS-MLT@CMC nanomicelles in NIR-Ⅱregion is outstanding with the extinction coefficient at 1270 nm of 20.73 L g^-1 cm^-1.FeS-MLT@CMC nanomicelles show the photothermal conversion efficiency of 26.56%,followed by stable photothermal performance.FeS-MLT@CMC nanomicelles are stable and highly dispersive in different biological media,and are biocompatible with red blood cells.FeS-MLT@CMC nanomicelles at lower concentration(15μg m L^-1)can generate obvious inhibitory effect towards gastric cancer cells.MLT can be controllably released to seriously kill tumor cells by photothermal effect,indicating that FeS-MLT@CMC nanomicelles can be controlled to release MLT by their photothermal effect.It is indicated that FeS-MLT@CMC nanomicelles can be used for efficient photothermal/immunoregulatory therapy,which provides a new way for targeting and delivering drug,and combination therapy for cancer.In summary,FeS@Au heterostructure and FeS-MLT@CMC nanomicelles were successfully synthesized,which have strong NIR-Ⅱabsorbance and excellent photothermal properties,and can be combined with other therapies in order to achieve NIR-Ⅱphotothermal enhanced multimodal treatment of tumor.Our researches broaden the potential applications of FeS nanomaterials in the biomedical fields.