Study On Nanoparticles For Targeted Fluorescent Imaging And Synergistic Treatment Of Malignant Tumor

Malignant tumor(generally known as cancer)is a new creature developed by normal cells in the body that mutate,grow and escape the elimination of the immune system,characterized by rapid growth,destruction of the surrounding tissues and distant metastases.With the incidence and mortality increasing year by year,it has become the leading cause of death for the people of our country.At present,the main treatment methods of malignant tumor are surgery,radiation and chemical therapy.Although with the comprehensive application of various treatments,the mortality of malignant tumor is declining year by year.However,these treatments are not accurate in clinical practice.Surgery can remove tumor lesions,but lacks the means of accurate imaging of tumors.It often requires extensive resection of tissues and organs,resulting in postoperative dysfunction and quality of life.Radiation therapy and chemical therapy are often lacking in targeting,destroying normal tissues and causing unnecessary complications while killing tumor cells.In addition,because conventional radiotherapy and chemotherapy can only kill common tumor cells,the killing effect on cancer stem cells is poor,which eventually causes recurrence and metastasis of tumor.Therefore,it is of great significance to study the target imaging and targeted cooperative therapy of tumor.Fluorescent polymer dots are emerging fluorescent nanomaterials in recent years.With good chemical,thermodynamic stability and good biocompatibility,it has potential application value in biological imaging.Therefore,in the second chapter of this paper,we synthesized the Polymer dots(PDs)by crosslinking the polyethyleneimine(PEI)and carbon tetrachloride(CTC).The size of the polymer dot is 15 to 100 nm by transmission electron microscopy,and it has a wider particle size distribution.The basic structure of PDs was confirmed to be the same as that of PEI by FTIR and XPS,and it was formed by crosslinking each amino group of PEI by carbon tetrachloride.The optimum excitation wavelength and emissionwavelength of PDs are 400 nm and 475 nm,respectively.We further interconnected the PDs and the Folic acid(Fa)by electrostatic action.Fluorescence spectroscopy showed that Fa had the effect of quenching PDs fluorescence.However,when the mass ratio of PDs to Fa was larger than 10:1,Fa had little effect on the fluorescence of PDs,so we chosed 20:1 to synthesize Fa@PDs.Fa@PDs has a stable fluorescence effect under the continuous light and the concentration of different ions.In vitro experiments have proved that Fa@PDs has small toxicity and has the role of targeted fluorescence imaging in KB cancer cells through the specific binding of folic acid to folic acid receptor.The experimental results of this part have laid the foundation for further study of targeted fluorescence imaging in oral cancer.The tolerance of cancer stem cells to chemotherapeutic drugs is an important cause of refractory malignant tumor,so the strategy of inducing differentiation of tumor stem cells to kill by chemotherapeutic drugs has a good prospect.Retinoic acid(Ra)can inhibit the proliferation of tumor stem cells and induce differentiation,which is the first choice for the treatment of tumor differentiation.However,the use of retinoic acid alone has the limitations of limited drug delivery,lack of targeting,and poor killing effect on common cancer cells.In order to overcome these shortcomings,in the third chapter,we transformed the retinoic acid molecule into a drug loaded targeting nanoparticle,and maintained its original functional activity.The experimental results show that the nanoparticles(Ferrocene retinoic acid nanoparticles,Fc)is water soluble and have uniform particle size,which is about 13.76nm;the nanoparticles with a positive charge,which is 24.6mv.It is sensitive to the high content of reduced glutathione(GSH)in the tumor cells,so can be instantly dissociate from the GSH,which can play a target role.In vitro experiments further showed that the functional activity of Fc nanoparticles was similar to that of Ra,which significantly inhibited the proliferation,migration and drug resistance of cancer stem cells,and reduced the expression of Oct4 and Sox2,and induced the differentiation of cancer stem cells.The above results indicate that the prepared Fc nanoparticles retain Ra functional activity and overcome the disadvantages of retinoic acid.It is a kind of targeted nanoscale that can inhibit the differentiation of tumor stem cells and has a good application prospect.In the fourth chapter,based on the previous chapter,We synthesized Ferrocene retinoic acid /Taxol nanoparticles(Ft).The nanoparticles are hydrophilic outside,theinner hydrophobic core of which carries paclitaxel,and the maximum drug loading rate is 16.7%.The particle has uniform size,with positive charge.The average particle size is 13.86 nm,and the average Zeta is 22.8mv.Ft is sensitive to GSH.In the presence of GSH,taxol is released immediately;In the absence of GSH,it is more stable.In vitro experiments have shown that Ft has a strong killing effect on KB cancer cells and low toxicity to normal cells.In vivo experiments showed that compared with simple Ra,Fc and Ta,Ft could play a synergistic effect and had the strongest tumor suppressor effect.And the toxicity of tissues and organs is small.The experimental results of this chapter show that the prepared Ft nanoparticles have a targeted synergistic anti-cancer effect and have good prospects for application.