Molybdenum Diphosphide Nanorods With Laser-Potentiated Peroxidase Catalytic/Mild-Photothermal Therapy Of Oral Cancer

Background:Oral squamous cell carcinoma（OSCC）is one of the most common malignancy in the oral and maxillofacial region.The available gold standard treatments for oral cancer,including surgery,radiation and chemotherapy generally fail to completely eradicate tumor while causing severe side effects.Moreover,the microbial floras in the oral cavity are rich and diverse,which not only affects the process of wound healing,but also develops the occurrence and development of cancer.Therefore,there is an urgent need to develop a minimally or non-invasive technology that simultaneously achieves effective tumor eradication and anti-infection mechanism offering a potent therapeutic effect.Recently,chemodynamic therapy（CDT）,as an emerging cancer therapy strategy,is closely combined with the tumor microenvironment（TME）.TME is a special environment where is different from normal tissues,mainly including slight acidity,hypoxia and overexpression of some substances（such as H₂O₂,glutathione,etc.）.It is found that these factors different from normal tissues provide necessary nutrients and conditions for tumor proliferation and metastasis.However,this feature also provides an important reference for the selectivity of tumor treatment and enhancing the effect of some treatment methods.CDT uses chemical agents containing iron ions to selectively catalyze the endogenous hydrogen peroxide（H₂O₂）of tumors by Fenton or Fenton like reaction,increase the concentration of hydroxyl radical（·OH）,and induce cell apoptosis or death,so as to achieve the therapeutic effect of anti-tumor.However,due to limitations of CDT itself,it failed to achieve the ideal effect.Purpose:we investigate a new nano-material,named molybdenum diphosphate nanorods（Mo P₂NRs）,which has peroxidase-like activity and photothermal properties.Under near-infrared light（NIR）irradiation,it is able to catalyze the endogenous H₂O₂of tumors,produce high concentration of·OH,and remarkably improve CDT performance.Methods:Mo P₂NRs were prepared through high temperature reaction and ultrasonication-assisted exfoliation.The morphology of Mo P₂NRs was visualized by scanning electron microscopy（SEM）and transmission electron microscopy（TEM）.The chemical composition of Mo P₂NRs was determined by energy dispersive X-ray spectroscopy（EDS）,which was taken on the SEM.The chemical composition and purity of the obtained products were analyzed by X-ray photoelectron spectroscopy（XPS）.The crystal phase and purity were analyzed by X-ray powder diffraction（XRD）analyses.The calculation of Mo P₂NRs of the extinction coefficient were measured by inductively coupled plasma atomic emission spectroscopy（ICP-AES）.The UV-vis-NIR absorption spectra were recorded using an ultraviolet-visible spectrophotometer.To quantitatively determine the photothermal conversion performance of Mo P₂NRs,we recorded the temperature curve of the NRs with different concentrations irradiated by a laser at the same power density,or the NRs with the same concentrations irradiated by a laser at different power density.The photothermal conversion efficiency and photothermal stability was also tested.The catalytic activity of decomposing H₂O₂（～100μM）at low concentration was detected by terephthalic acid（TA）fluorescence method.Finally,to confirm the inhibitory effect on oral squamous cell carcinoma and antibacterial activity of nanoparticles,we designed a series of in vitro experiments to evaluated the cell toxicity and anti-tumor effect using CAL27 and SCC9 cells,and antibacterial activity using E.coli and S.aureus bacteria.The orthotopic CAL27 oral cancer tumor model was established to observe the therapeutic effect against cancer,and to study the anti-cancer mechanism of NRs.Results:The as-obtained Mo P₂NRs have rod-like shapes with uniform diameter,good dispersibility and biocompatibility.The Mo P₂NRs demonstrated strong optical absorption in NIR region and simultaneous favorable photothermal properties.When irradiated with 808 nm laser,Mo P₂NRs could act as photosensitizers to efficiently capture the photo-excited band electrons and valance band holes,exhibiting an enhanced peroxidase-like catalytic activity for decomposition of tumor endogenous H₂O₂to·OH.·OH is a kind of reactive oxygen species,which has stronger oxidative damage ability than H₂O₂or superoxide anion in reactive oxygen species.High level of·OH subsequently destroy the cellular biomacromolecules both in tumor cells and bacteria,and cause irreversible damage to cells,and simultaneously achieve effective tumor eradication and anti-infection.The corresponding experiments in vitro and in vivoconfirmedthelaser-potentiatedsynergisticperoxidase catalytic/mild-photothermal therapy that generated abundant·OH both in tumor cell and bacteria,thereby displaying notable inhibitory effects.Moreover,the anti-cancer therapeutic mechanism investigation suggested that·OH induced mitochondrial apoptosis may be a dominant death signaling pathway to fight against oral cancer cells.Conclusion:we develop an 808 nm laser-potentiated peroxidase catalytic/mild-photothermal therapy of molybdenum diphosphide nanorods（Mo P₂NRs）to improve CDT performance,and increase the·OH production of tumor.As demonstrated both in vitro and in vivo,this system exhibits a superior therapeutic efficiency with inappreciable toxicity.Hence,our work presented an innovative and multifunctional therapeutic modality,showing unique advantages in oral cancer therapy.