Study On The Inhibitory Effect Of BaGdF₅:Yb³⁺,Er³⁺ Mediated Photodynamic/Chemotherapy On Breast Tumor

Cancer treatment has always been a difficult problem in the scientific community,and the number of new cases and deaths are increasing year by year due to factors such as environment,population and lifestyle.It is estimated that the number of global cancer patients will increase from 17 million in 2018 to 26 million by 2040.It can be seen that the clinical treatment of tumors has always been one of the key and difficult points in the field of biomedical research.At present,the clinical treatment of tumor mainly includes surgery,chemotherapy and radiotherapy.However,these traditional treatments not only kill tumor tissue,but also destroy the immune system to a certain extent,and even cause tumor recurrence and metastasis,thus bringing some side effects to patients.At present,photodynamic therapy（PDT）has also been widely used and studied,which can reduce the side effects of conventional therapy and make up for the defects such as chemotherapy,but there are some limitations in PDT treatment because of the low penetration depth and difficult delivery of single photosensitizer.The photodynamic therapy after the conversion of nanomaterials into matrix materials loaded with photosensitizers can improve the above shortcomings.At the same time,the study of combined chemotherapy and photodynamic therapy has been widely used.For this reason,this subject mainly established more than one conversion nanomaterial as the carrier to study the combination of chemotherapy and photodynamic therapy after loading chemotherapeutic drugs and photosensitizers.In this study,Methoxy polyethylene glycol amino（m PEG-NH₂）modified upconversion nano-matrix material Ba Gd F₅:Yb³⁺,Er³⁺（Upconverting nanoparticles,UCNPs）with good biocompatibility was synthesized by one-pot hydrothermal synthesis.The results of X-ray diffraction and transmission electron microscope showed that the synthesized UCNPs had cubic phase structure and good dispersion.The results of upconversion emission spectra show that under the laser irradiation of980 nm,the electron transition occurs due to the doping of lanthanide Er³⁺ions,resulting in green emission and red emission.The above results can prove the successful synthesis of UCNPs.Using UCNPs as the precursor,paclitaxel（PTX）was linked to the surface of UCNPs to form UCNPs-PTX,by diamonium coupling reaction,which is the result of the interaction between the amino group of PTX and the amino group of m PEG.The successful loading of PTX can be proved by Fourier transform infrared spectroscopy（FTIR）.Finally,using UCNPs-PTX as the precursor material,dihydroporphine e6（Ce6）was connected to UCNPs-PTX through the covalent grafting reaction between its carboxyl group and the amino group of m PEG to synthesize UCNPs-PTX-Ce6.The successful loading of Ce6 can be proved by FTIR spectrum and UV-visible absorption spectrum（UV-Vis）.The material enhances the tissue penetration depth of photosensitizer in photodynamic therapy.In this study,mouse breast cancer cell line 4T1 was used as a cell model to detect the inhibitory effect of UCNPs-PTX-Ce6 on cell proliferation by cell proliferation、apoptosis、reactive oxygen species and mitochondrial membrane potential test.The results showed that UCNPs-PTX-Ce6 drug treatment group showed lower cell proliferation activity,higher apoptosis rate,higher production of reactive oxygen species and greater change of mitochondrial membrane potential under near infrared radiation（NIR）.Then,Kunming female mice implanted with mouse breast cancer cell line 4T1 were used as the model of anti-tumor activity in vivo,and the tumor-bearing mice were divided into groups under the action of PBS、NIR、UCNPs、UCNPs-PTX-Ce6、UCNPs+NIR and UCNPs-PTX-Ce6+NIR,respectively.The tumor inhibitory effect of UCNPs-PTX-Ce6 in vivo was verified by the indexes of body weight、tumor volume and tumor weight of mice.The results showed that the body weight of mice in each drug treatment group did not decrease,and compared with the blank control group and no light treatment group,the tumor volume of UCNPs-PTX-Ce6+NIR drug treatment group decreased significantly,and the tumor weight was the smallest.To sum up,according to the above in vitro and in vivo test results,it can be concluded that the synthesized UCNPs matrix materials have good biocompatibility and low toxicity.At the same time,under the irradiation of laser,UCNPs-PTX-Ce6can improve the therapeutic effect of single chemotherapy,and achieve the goal of UCNPs-mediated photodynamic/chemotherapy effect on breast tumor inhibition.