Design Of Molybdenum Disulfide Nanoparticles For Tri-negative Breast Cancer

The incidence and mortality of breast cancer ranks first among female cancers worldwide^[1].Among them,triple negative breast cancer（TNBC）is not sensitive to the specific targeting and hormone therapy currently available due to the lack of common expression receptors of other types of breast cancer,resulting in poor therapeutic effect,high invasiveness,and high metastasis rate.Therefore,the treatment of patients with TNBC remains the biggest challenge in the treatment of breast cancer.Here,we developed a tumor-targeting ligand penetrating peptide LNP-modified and PEI-grafted molybdenum disulfide（MoS₂）nanoflower as a reagent for photothermal therapy and photodynamic therapy,as well as p H response and light triggering.A released drug delivery vehicle for the combined treatment of triple negative breast cancer.The synthesized MoS₂has a 3D flower-like structure with uniform size and negatively charged in aqueous solution（-28 m V）.It can achieve high-efficiency loading of drugs through its multi-layered fold structure andπ-πinteraction with chemotherapeutic drugs,with a strong photothermal conversion capability.Nuclear magnetic resonance（NMR）results indicated that LNP and Mal-PEG-NHS and PEI could be covalently bind to form LNP-PEG-PEI（PPL）.After PPL coating on MoS₂-DOX（MoS₂-DOX@PPL）nanoflowers have good water dispersibility and photothermal stability,and can achieve NIR trigger release and acid response release of chemotherapeutic drugs under the dual action of near-infrared photothermal stimulation loose and intracellular H⁺pump.In vivo fluorescence imaging,photothermography and photoacoustic imaging via observing the accumulation of MoS₂whether there is of LNP polypeptide in tumor regions in triple negative breast cancer 4T1 tumor-bearing mice,indicating that LNP ligands have high accumulation capacity.MoS₂-DOX@PPL was positively charged,through electrostatic adsorption combined with negatively charged cells and the action of transmembrane peptides,resulting in more accumulation of tumor areas.The detection of 4T1 cell viabiity by CCK-8,the combination of peroxidase-likeaction（POD）-chemotherapy-photothermal-photodynamics of MoS₂-DOX@-PPL significantly increased inhibition of proliferation of 4T1 cells compared to the single treatment.Therefore,in addition to traditional chemotherapy,MoS₂-DOX@PPL has a catalytic effect similar to peroxidase-like（POD）,which can catalyze the production of hydroxyl radicals by hydrogen peroxide in the tumor areas,and can be controllable production of reactive oxygen species（ROS）such as singlet oxygen to kill tumors under irradiated by near-infrared light（NIR）.It indicates that 3D MoS₂nanoflowers provide a highly efficient platform for tumor combination therapy.