The Preparation Of A Novel FA-BSA-PEG/MoOx Nanosheet And Study On Breast Cancer Combined With Chemo-Photothermal And Immunotherapy

Cancer is one of the leading causes of death worldwide,and it is estimated that there are 19.3 million new cases and nearly 10 million cancer deaths in the world occurred in 2020.Among them,breast cancer has surpassed lung cancer as the most common cancer,accounting for about 11.7%of the new cases.Traditional cancer treatments mainly include:chemotherapy,radiotherapy and surgery,but there are many problems still exist,and the cancer has not been eradicated,such as the server side effects,drug resistance,potential healthy issue under radiation,after surgical treatment.Therefore,there is an urgent need to develop a multifunctional carrier to solve all the above issues and finally conquer this nut.Photothermal therapy(PTT)has become a hotspot in recent years due to its non-invasive and high targeting properties.The special photothermal agents could convert the light into heat energy and cause the hyperthermia,which will trigger several hazardous phenomena,such as denaturation of proteins,lysis of cell membrane,evaporation of cytosol,thereby leading to cell death.In addition,PTT can also induce immunogenic cell death(ICD),release tumor associated antigens(TAAs)and damage associated molecular patterns(DAMPs),and activate the immune response.Based on these merits,this paper designed and prepared a multifunctional molybdenum oxide nano sheet with strong near-infrared absorption,good biocompatibility,high efficiency of photothermal conversion,which was used in breast cancer combined with chemo-photothermal and immunotherapy.The molybdenum oxide is prepared by a hydrothermal method,the nanosheets are dispersed in cyclohexane,and the single-layer molybdenum oxide nanosheets are mechanically peeled off under the ultrasonic probe.It was further functionally modified with lipoic acid-polyethylene glycol complex(LA-PEG)and folate-albumin complex(FA-BSA)to prepare a new type of molybdenum oxide nanosheet FA-BSA-PEG/MoOx with excellent water solubility.And docetaxel(DTX)was selected as a model chemotherapeutic drug loaded on the surface of molybdenum oxide nanosheets for chemotherapy-photothermal co-therapy.Transmission electron microscope(TEM)and atomic force microscope(AFM)results that FA-BSA-PEG/MoOx is a single-layer sheet structure with a thickness of about 2-5 nm.The dynamic light scattering method(DLS)measured that the particle size of the nanosheets was about 80 nm,and the Zeta potential was-17mv.The nanosheets can be uniformly and stably dispersed in a variety of media,and the hemolysis rate is less than 5%,indicating that the nanosheets have good hemocompatibility.The result of photothermal effect investigation shows that FA-B SA-PEG/MoOx nanosheets could cause a fast temperature increase,with a photothermal conversion efficiency of 43.41%.It is an excellent photothermal agent and has the potential of photothermal therapy in the biomedical field.Nanosheets also showed pH-dependent degradation characteristics,which are stable under acidic conditions and rapidly degrade under neutral or alkaline conditions,avoiding accumulation in normal tissues and causing toxicity.DTX can be loaded in the FA-BSA-PEG/MoOx nanosheet effectively with the maximum drug loading of 76.49%.The drug release behavior is also related to the degradation characteristics of the nanosheets.In the release media of pH 5.0 and pH 7.4,the cumulative drug release after 60 h is 42.08%and 77.01%,respectively.Human breast cancer cell(MCF-7)was selected as model to study the anti-tumor effect of FA-BSA-PEG/MoOx in vitro.Cytotoxicity experiments and uptake experiments show that nanosheets can be effectively taken up by cells and exhibit stronger cytotoxicity under the near-infrared light.The polarization of macrophages in vitro indicates that FA-BSA-PEG/MoOx+NIR can alleviate the tumor immunosuppressive microenvironment.Calreticulin(CRT)exposure and heat shock protein 70(HSP70)expression verified that FA-BSA-PEG/MoOx@DTX nanosheets can induce tumor immunogenic death(ICD).The anti-tumor effect in vivo was studied and the results show that nanosheets can not only inhibit the growth of tumors in situ and distal tumors,but also inhibit tumor metastasis to the lungs.This is attributed to the chemo-photothermal combination therapy,as well as ICD and the microenvironment that relieves tumor immunosuppression.In summary,the FA-BSA-PEG/MoOx nanosheets have the advantages of good biosafety,biocompatibility,etc.,and can realize the synergistic anti-tumor effect of chemo-photothermal and immunotherapy at the cellular level and the animal level,and It can be rapidly degraded and discharged in the body to avoid accumulation,which provides an excellent research foundation for the chemo-photothermal immune synergistic therapies.