Combinatorial Discovery Of Mo-based Polyoxometalate Clusters For Tumor Photothermal Therapy And Normal Cell Protection

Funkhouser first proposed the term "theranostic" in 2002,that is,the integration of diagnosis and treatment,which is defined as a compound system of medicines that integrates disease diagnosis and treatment.In the process of tumor photothermal therapy,in order to improve the sensitivity of nanomaterials in vivo tracking and tumor treatment effect,multimodal imaging-guided combined therapy has become a new development trend.Nanomaterials with multiple functions(such as precise diagnosis,therapeutic efficacy,and biosafety)are attractive for tumor treatment,but they are still a technical challenge.In this paper,by improving the Folin-Ciocalte method,a dark green and transparent appearance of molybdenum(Mo)-based polyoxometalate clusters(Mo-POM)were prepared,in which gallic acid can also be used as a stabilizer.In this paper,by improving the Folin-Ciocalte method,a dark green and transparent appearance of molybdenum(Mo)-based polyoxometalate clusters(Mo-POM)were prepared,in which gallic acid can also be used as a stabilizer.The Mo-POM was studied through various characterizations,and the best conditions for the synthesis of Mo-POM were selected by the ultraviolet-visible absorption spectrum.Mo-POM is water-soluble measured by some characterization methods such as transmission electron microscopy and hydrated particle size,and is easy to be synthesized on a large scale.It can maintain high stability for more than 30 days even in high ionic strength media.Using 808 nm laser to irradiate Mo-POM solution under different conditions,it is determined that Mo-POM has a fairly high photothermal conversion efficiency(about 56.6%)and excellent photothermal stability.Use the standard SOD(superoxide dismutase)assay kit and ABTS(2,2’-azinobis(3-ethylbenzothiazoline 6-sulfonyl fluoride)radical cation decolorization assay to obtain Mo-POM Remove active oxygen.It has laid a solid foundation for the subsequent combined diagnosis and treatment of tumors in vivo and in vitro.Carry out in vivo and in vitro tumor studies on monodisperse Mo-POM.The anti-tumor efficacy of the nano-medicine was preliminarily studied through handheld thermal imaging device,in vitro cell experiment,in vivo anti-tumor experiment and inductively coupled plasma mass spectrometer.By studying the in vivo photothermal conversion effect of the nanomedicine,the cell survival of cells in vitro,the cell killing effect after laser irradiation,the anti-tumor ability of cells in vitro,and the anti-toxic ability of mice in vivo,preliminary exploration of its effect on tumor treatment.The test results show that in the tumor microenvironment,monodisperse Mo-POM gathers at the target site and induces tumor thermal ablation after absorption in the near infrared(NIR).Mo-POM has fast blood clearance ability.Ultra-small particles can evade recognition and capture by the liver,and are cleared by the kidneys.In addition,Mo-POM effectively eliminates reactive oxygen species(ROS)through the charge transfer between Mo(VI)and Mo(V)states,thereby avoiding off-target effects on normal cells and improving the treatment efficiency in vivo and in vitro.In addition,COF has the advantages of highly porous structure,high drug loading and good thermal stability.The original tank method was used to synthesize heteropoly blue and COF in situ.The successful preparation of heteropoly blue was characterized by ultraviolet spectrophotometer and Fourier transform infrared spectrometer.Through transmission electron microscopy,scanning electron microscopy,particle size and Zeta potential analyzer,X-ray diffraction,specific surface area and porosity analyzer,hand-held thermal imager,the structure and properties of the bio-nanopharmaceutical system were preliminarily studied.The properties of HPB@COF in the tumor microenvironment are simulated by studying the controllable drug release ability of the nanomedicine and the in vitro photothermal conversion effect.According to the experimental results,it can be seen that the stability of the successfully synthesized HPB@COF is good,and its particle size is about 200 nm.In addition,the pH-responsive HPB@COF has good drug release under acidic conditions.Finally,HPB@COF has high photothermal conversion efficiency and is a good photothermal nanomaterial,laying the foundation for future anti-tumor experiments in vivo and in vitro.