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Experimental Study Of Multifunctional Nanomaterial Drug Loading System In Accurate Diagnosis And Targeted Therapy In Cervical Cancer And Endometrial Cancer

Posted on:2022-01-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:S YaoFull Text:PDF
GTID:1484306608480234Subject:Oncology
Abstract/Summary:PDF Full Text Request
According to the latest statistics of the American Cancer Society,at least 8 million people have died of cancer worldwide in 2020,and the incidence and mortality rates are on the rise year by year.It is estimated that by 2030,the number of people dying of cancer worldwide will reach 13 million.Gynecological tumors occur in the female reproductive organs,mainly including cervical,endometrial and ovarian cancers.Gynecological malignant tumors are characterized by multiple pathological types,different clinical outcomes,different prevention and treatment methods.Different from solid tumors from other organs,tumor outcomes of gynecological tumors are not only related to patients,but also involve their offspring.Therefore,in a sense,gynecological tumors face more severe challenges.Gynecological tumors have many problems,such as high morbidity,high mortality,insensitivity to chemotherapy and poor prognosis,which brings great challenges to women's life and health.The incidence of cervical cancer is highest among female malignancies,but with the spread of HPV vaccine and pre-cervical cancer screening,the incidence and mortality of cervical cancer have declined in part.Endometrial cancer is characterized by typical early symptoms and sensitivity to chemoradiotherapy,so most patients have an early prognosis and perfect therapeutic effect.In recent years,despite the continuous improvement of surgical techniques for female reproductive system tumors,the wide application of laparoscopy,and the continuous application of new chemotherapy drugs,chemotherapy regimens and small-molecule targeting agents,these traditional treatment methods have not significantly improved the long-term survival rate of patients.The principle of treatment for patients with recurrent cancer is palliative treatment(surgery as an adjunct treatment),and their therapeutic value has not been confirmed.Therefore,how to reverse chemotherapeutic drug resistance,target tumor cells,reduce surgical trauma the toxic and side effects of chemotherapeutic drugs is an urgent problem for clinicians to solve.Therefore,there is an urgent need for new and effective therapeutic methods to improve the prognosis of patients.Nanotechnology emerged in the early 1990s,and has been applied in many fields(aerospace,biomedicine,materials,etc.),and has achieved rapid development.Similarly,the development of nanomedicine technology has provided unlimited possibilities for the diagnosis and treatment of a variety of diseases,and nanomedicine drug delivery system has realized the targeted delivery of anti-tumor drugs,improving efficacy and reducing toxicity.The development of nanomedicine technology has the following application advantages:1)nanomaterials,as drug carriers,significantly increase their solubility,reduce the toxic and side effects of drugs and improve the utilization of drugs;2)Massive neovascularization,increased permeability and absence of lymphatic drainage in tumor tissues.The enhanced permeability and retention effect(EPR effect)of tumor tissue is the basis of passive targeting and slow release effect of nanomaterials.3)Nanoparticles has many characteristics,such as large surface area of easy modification,on its surface coupling with tumor targeted small molecules(folic acid,glucose molecules,etc.),through the nano materials on the surface of small molecules combine with the tumor cell surface corresponding ligand specificity,increase the nanoparticles assembled at the tumor site specificity,so as to realize the active targeting characteristic of the nanometer carrier;4)Fe3O4(Ferroferric Oxide)has magnetic targeting characteristics under the action of external magnetic field,and produces magnetic hyperthermia(MH)and reactive oxygen species(ROS)under the alternating magnetic field,which increases the killing ability of tumor tissue of nanomaterials;5)Local injection of gold nanoparticles has the characteristics of lymphatic targeting,radiotherapy sensitization and CT(Computed Tomography)imaging sensitization,which improves the accuracy of tumor diagnosis and increases the killing effect of tumor tissue.Based on the characteristics of passive targeting,magnetic targeting and active targeting,the nanocarriers can be specifically identified and applied to tumor tissues through the synergistic effect of multiple targeting.The synergistic effects of chemotherapeutic drugs,magnetic heat and reactive oxygen induced apoptosis of tumor cells and radiotherapy sensitization of gold nanoparticles enhance the killing ability of tumor.In addition,trioxide and gold nanoparticles as contrast agents showed good contrast effect in MRI and CT detection,respectively,which provided a possibility for preoperative diagnosis of tumor patients.Based on the imaging sensitization of multifunctional nanocarriers,the targeted regulation mechanism improves the diagnostic accuracy and targeted tumor killing ability of tumor patients.In this paper,based on the clinical actual demand,the female patients with malignant tumor diagnosis and chemotherapy drug resistance,problem such as the lack of targeted tumor therapy,around the two most common types of malignant tumor,women integrated use of features,tumor targeting killing effect of nanometer carrier sensitization and radiotherapy sensitization and imaging characteristics of the multifunctional nanomaterials in cervical cancer and endometrial carcinoma accurate diagnosis and targeted treatment application fully discusses,mainly for the innovative as follows:(1)Preparation of multifunctional magnetic drug-carrying nanocarriers and experimental study on their application in the diagnosis of cervical cancer and targeted tumor killing;(2)Development of multi-functional targeted gold nanoparticles and experimental study on their application in endometrial cancer imaging sensitization and radiotherapy sensitization.Part? Preparation of magnetic nanoparticles for the diagnosis and the experiments study of targeted tumor killing effect for cervical cancerResearch purposeCervical cancer is the fourth most common cancer among women,with about 570,000 cases diagnosed and 311,000 deaths worldwide in 2018.While in China,cervical cancer has a particularly high incidence,with 106,000 cases diagnosed and 48,000 deaths,due to limited screening and lack of universal vaccine.At present,surgery is the main treatment for early cervical cancer,while patients with medium-and late-stage are treated by concurrent chemoradiotherapy.However,traditional chemotherapy has some disadvantages,such as lack of tumor targeting,high toxicity and low therapeutic efficiency.Based on the above shortcomings,the traditional diagnosis and treatment scheme can not significantly improve the prognosis of patients and significantly prolong the survival time of patients.In order to overcome these shortcomings,a multifunctional magnetic nano drug delivery system with low toxicity and high killing efficiency was prepared in this project.The aim of this research is to focus on clinical problems and advanced academic progress,which is based on pegylated glyco-ploylactic acid(PEG-PLA-NP)nanomaterials,which are integrated with various properties of other materials.To explore the feasibility of the multi-functional magnetic nanomaterial for preoperative accurate diagnosis of cervical cancer and targeted tumor killing treatment.Research methods1.Preparation and physical and chemical properties of multifunctional magnetic nanoparticles:Fe3O4 with magnetic targeting was prepared from FeCl3-H2O.A multifunctional integrated probe for diagnosis and treatment based on PEG-PLA-FITC polymer micelle was prepared by emulsification method.Oil-soluble Fe3O4 nanoparticles and doxorubicin(DOX)were coated in the oil phase of PEG-PLA-FITC micelles.The DOX-Fe3O4-PEG-PLA-NP multifunctional nanocarrier was prepared for the study of nuclear magnetic resonance MRI imaging sensitization and targeted tumor killing in tumor-bearing mice.Common Fe3O4,PEG-PLA-NP and DOX-PEG-PLA-NP nanomaterials were prepared as controls.Transmission electron microscopy,particle size laser scatterometer,MRI and fluorescence spectrophotometer were used to detect the physical and chemical properties of particle size.2.Verification of the effect of targeted killing and sustained release of tumor cells:in vitro,the cumulative release of different groups of nanoparticles under different pH conditions was investigated by High Performance Liquid Chromatography(HPLC).MTT assay was used to investigate the killing effect of different groups of nanoparticles incubated for different time on tumor cells.Cell function assay(scratch assay,Transwell assay and flow cytometry assay)was used to investigate the effects of different nanoparticles on the invasion,migration and apoptosis of tumor cells.Cell uptake experiment was conducted to explore the targeted uptake ability of multifunctional magnetic nanoparticles to cervical cancer cells in vitro.3.Verification of in vivo slow release effect and tumor targeted killing effect:SD rats were injected with different kinds of nanomaterials through tail vein,and DOX alone was used as negative control.Blood was collected from the inner canthus at different time points,and plasma DOX content at different time points was detected by HPLC,pharmacokinetic map was drawn,and drug half-life(t1/2)of different groups was obtained.The mouse models of abdominal cavity and subcutaneous tumor bearing were established as in vivo experimental research objects.After different groups of magnetic nanoparticles(control group was DOX group)were injected through tail vein,the animals were killed at different time points,and the tumor tissues and other organs were extracted.The distribution of drug tissues was detected by high performance liquid chromatography(HPLC)to determine the distribution characteristics of multi-functional magnetic nanoparticles in the organs of mice.Subcutaneous tumor-bearing mouse model was established,and different drug groups were injected into tail vein.The body weight and tumor volume of the nude mice were measured at different time points,and the tumor growth curve was plotted.After the completion of the treatment cycle,the nude mice were euthanized,and different tissues were stained with H?E,TUNEL and Ki67 to investigate the effects of different treatment groups on the apoptosis,invasion and migration of tumor tissues.The survival curve was drawn by the survival of tumor-bearing mice to explore the effect of magnetic nanoparticles on the survival of tumor-bearing mice.Second generation sequencing and proteomic detection were performed on tumor tissues of different treatment groups to further explore the molecular mechanism and related pathway changes of tumor killing caused by magnetic nanocarriers.4.Verification of multifunctional nanoparticle imaging sensitization in vitro and in vivo:the relationship between sample concentration and signal intensity was explored by NMR testing at different concentrations in different treatment groups,and the concentration signal intensity curve was drawn to obtain the T2 relaxation rate in different groups.Subcutaneous tumor-burdened mice model was constructed by tail vein injection of different group of magnetic nanomaterials,different time point detection of nuclear magnetic resonance T2 like signal strength,get different magnetic nanoparticles effect time in vivo magnetic resonance imaging sensitization effect diagram,clear multifunctional magnetic nanoparticles sensitization characteristics,preoperative imaging evaluation of multifunctional magnetic nanoparticles drug delivery system as MRI contrast agent.Research results1.The multifunctional magnetic nanoparticles preparation and the pHysical and chemical properties testing:successful preparation of tumor magnetic targeted multifunctional magnetic drug-loading nanoparticles and ferroferric oxide particle size in about 20 nm,multifunctional magnetic nanoparticles size(DOX-Fe3O4PEG-PLA-NPa)around 120 nm,transmission electron microscope to uniform particle size,good dispersion,potential for-5 mV.UV spectrophotometry and fluorescence detection confirmed that DOX and Fe3O4 were successfully encapsulated into 18 PEG-PLA nanocarriers.The encapsulation rate and drug loading were 34.9%and 3.8%,The encapsulation rate and drug loading of DOX-PEG-PLA-NP were 23.7%and 2.6%,respectively,which met the requirements of subsequent biological experiments.2.Verification of targeted killing and sustained release effect of tumor cells in vitro:in vitro drug release experiment results showed that under the same environment,the cumulative release amount of the nanocarrier group was lower than that of the drug group alone(p<0.05),and the release curve of the nanocarrier group was relatively stable in vitro.Interestingly,the cumulative release of the nanoscale at pH 6.5 was 1.5 times higher than that under neutral conditions.In vitro release experiments show that multifunctional magnetic nanoparticles have certain pH-sensitive properties and slow-release effect.MTT assay results showed that the cell toxicity of PEG-PLA nanoblocks was not significantly enhanced with the increase of the concentration of PEG-PLA nanoblocks.When the concentration of PEG-PLA nanoblocks reached 100 ?g/mL and the cells were incubated with HeLa cells for 72 h,the cell viability was still 60%.It is further proved that the PEG-PLA nanoblock copolymer we selected has low toxicity.Under the DOX dose of 4?g/mL(72 h,AMF),the inhibition rates of DOX,DOX-PEG-PLA-NP and DOX-Fe3O4-PEG-PLA-NP on cells were 69.03%,54.80%and 59.02%,respectively(p<0.05).Under the alternating magnetic field,the inhibition rates of DOX,DOX-PEG-PLA-NP and DOX-Fe3O4-PEG-PLA-NP on cells were 77.38%,80.18%and 88.04%,respectively(p<0.05).These results proved that alternating magnetic field treatment can significantly improve the killing effect of magnetic nanoparticles on tumor cells.The cytotoxicity of the material was positively correlated with incubation time and drug concentration.Cell function experiments showed that magnetic nanoparticles effectively reduced the proliferation and migration ability of tumor cells,and alternating magnetic field promoted the apoptosis of tumor cells.Cells to absorb the experimental results showed that under the external magnet attract,magnetic nanoparticle carrier by tumor cells intake is 2 times without magnet effect.The free DOX group reached peak uptake at 2 h,while the DOX-PEG-PLA-NP group reached peak uptake at 4 h.Under the magnetic field,the DOX-Fe3O4-PEG-PLA-NP group uptake reached its peak at 1 h.Those results confirmed that nanoparticles in vitro slow-release effect and tumor magnetic targeted features.3.Verification of in vivo sustained-release effect and tumor targeted killing effect:In vivo pharmacokinetic results showed that the half elimination time(t1/2)of DOX-Fe3O4-PEG-PLA-NP and DOX-PEG-PLA-NP were 15.92 h and 13.47 h,respectively,which were significantly longer than those of free DOX group(6.41 h,p<0.05).The area below DOX-Fe3O4-PEG-PLA-NP and DOX-PEG-PLA-NP suites were 159.81 ?g/mL/h and 132.72 ?g/mL/h(p>0.05),respectively.It was about 3 times that of free DOX group(43.78 ?g/mL/h)(p<0.05).The slow-release effect of the magnetic nanocarrier designed by the research group was demonstrated again in vivo.In vivo tissue distribution experiment results showed that the content of nanomaterial in tumor tissue was much higher than that of drug group alone,and under the action of external magnet,magnetic nanomaterial gathered the most in tumor site,which was 2.7 times that of drug group alone.In addition,the peak time of DOX group was about 2 h in different tissues,while the peak time of nano group was about 4-12 h.The above results again confirm the magnetic targeting and sustained-release properties of nanocarriers.In vivo trials of anti-tumor efficacy showed that The tumor size of DOX-Fe3O4-PEG-PLA-NP group(AMF)was 299.09 ±3.76 mm3,much smaller than that of DOX-Fe3O4-PEG-PLA-NP group(no AMF)(325.07 ± 7.09 mm3,p<0.05),DOX-PEG-PLA-NP(AMF)group(421.78 ±10.01mm3,p<0.05),DOX group(577.22±11.99mm3,p<0.05)and control group(748.12±22.58mm3,p<0.05).Subcutaneous tumors of tumor-bearing mice were significantly reduced in DOX-Fe3O4-PEG-PLA-NP group under alternating magnetic field treatment,while there was no significant difference between DOX-Fe3O4-PEG-PLA-NP and DOX-Fe3O4-PEG-PLA-NP group(p>0.05).Compared with the control group,all treatment groups had significant anti-tumor effect(p<0.05).According to the tumor volume,DOX-Fe3O4-PEG-PLA-NP group has a strong anti-tumor effect.The tumor volume inhibition rate of DOX-Fe3O4-PEG-PLA-NP group was 60.02%,about 1.37 times of DOX-PEG-PLA-NP(AMF)group(43.62%)and 2.5 times of free DOX group(22.84%).The results of H?E staining showed that the morphology of each tissue did not change significantly,which confirmed the low toxicity of nanocarriers.Tunel and Ki67 staining results showed that the mechanism of tumor tissue killing by magnetic nanocarrier was to promote the apoptosis and iron death of tumor cells.Sequencing and proteomics results of tumor tissue also demonstrated that magnetic nanocarrier enhanced the killing effect of tumor cells by promoting tumor cell apoptosis and iron death molecular pathways.4.In vivo and in vitro multifunctional nanoparticle imaging sensitization verification:T2 relaxation rate curves were drawn at different concentrations and different time points in vitro.The results showed that the T2 relaxation rate of the designed multifunctional magnetic nanocarrier was much higher than that of the control group and the standard substance,which proved that the magnetic nanocarrier had more sensitive MRI imaging properties.In vivo imaging results showed that the magnetic nanocarrier signal was weakened in MRI,and the intensity of the signal was negatively correlated with the concentration and time.Conclusions1.The multifunctional magnetic nanoparticles developed in this project have the characteristics of tumor targeting?slow release effect?low toxicity and degradability;2.Multifunctional magnetic nanoparticles inhibit the migration and invasion ability of tumor cells and promote tumor cell apoptosis;3.Multi-functional magnetic nanoparticles can promote cell apoptosis and produce reactive oxygen species through the synergistic effect of magnetic heat to improve the tumor killing effect;4.Multi-functional magnetic nanoparticles have good MRI sensitization effect,which is expected to be used as MRI contrast agent for solid tumors including cervical cancer,and be used in imaging diagnosis.Part ? Development of multifunctional targeted gold nanoparticles and their application in endometrial cancer imaging sensitization and radiotherapy sensitizationResearch purposeEndometrial cancer is typical,with 60%of patients diagnosed in the early stages of the disease(FIGO stage I)and a five-year survival rate of 80%.Patients with early-stage endometrial cancer received comprehensive staging surgery.patients who were intolerant to surgery were preferred to external radiation therapy and/or vaginal brachytherapy;and patients who were intolerant to surgery and radiotherapy were preferred to hormonal therapy.However,traditional treatments did not significantly improve patient outcomes.Preoperative imaging diagnosis lacks specificity and conventional postoperative treatment cannot significantly improve the prognosis of patients.Focusing on clinical problems and cutting-edge academic progress,this paper intends to take gold nanoparticles as the basis platform and fully integrate their various characteristics to study the feasibility of targeting gold nanoparticles for the diagnosis and treatment of endometrial cancer.Gold nanoparticles themselves have lymphatic targeting,CT imaging sensitization and radiotherapy sensitization characteristics.The coupling of PEG on the surface of gold nanoparticles can improve the stability of gold nanoparticles and reduce the absorption of reticuloendothelial system.Active targeting of tumor cells was achieved by coupled glucose molecule,and real-time fluorescence imaging of tumor tissue was achieved by coupled indocycanine green molecule."All in one" is the unique advantage of nanomaterials.The multifunctional gold nanoparticles prepared in this project are expected to realize the integration of tumor diagnosis and treatment,accurate preoperative imaging imaging evaluation of the condition.Real-time fluorescence imaging of intraoperative tumor tissue can realize accurate surgical resection.Targeted sensitization radiotherapy can be applied to micro-lesions after operation to improve efficacy and reduce toxicity.In the end,this project hopes to achieve accurate antitumor therapy based on accurate lymphatic and tumor imaging,which is in line with the latest diagnosis and treatment concept of "Theranostics" for malignant tumors.Research methods1.Preparation of multifunctional gold nanoparticles and detection of physical and chemical properties:gold nanoparticles were prepared by nitrite reduction method with tetrachloroauric acid as raw material.Gold Nanoparticles(GNPS)with appropriate particle size(20 nm)were prepared by controlling the reaction conditions.Glucose modified polyethylene glycol(PEG)nanoparticles(Glu-PEG-GNPs)were prepared by coupling PEG and Glucose molecules on GNPs surface.Indocyanine Green(ICG)molecule was coupled at the end of PEG molecule to prepare inddocyanine Green and glucose modified polyethylene glycol nanoparticles(Glu-ICG-PEG-GNPs).Normal gold nanoparticles(GNPs),PEG-GNPs and Glu-PEG-GNPs were prepared as controls.The physical and chemical properties of multifunctional gold nanoparticles,such as particle size,potential and composition,were detected by transmission electron microscopy,ICP-MASS and XPS.2.In vitro endometrial cancer targeted validation:screening of high glucose receptor expression of endometrial cancer cells(ISK)as a follow-up study object,and build the silence and the expression of cell line as the control group,together with the different kinds of the preparation of the nanometer gold particles incubation,cell uptake experiment clearly multifunctional nanometer gold particles of endometrial cancer cells in vitro targeting property.A mouse model of abdominal cavity bearing tumor was established as an in vivo experimental research object.After different groups of gold nanoparticles were injected through tail vein,tumor-bearing mice were killed at different time points,and tumor tissues and other organs were extracted.The distribution characteristics of the tissues in the body of gold nanoparticles were explored by ICP-MASS detection technology,and the tumor targeting property of multifunctional gold nanoparticles in vivo was contrastive analyzed to clarify the optimal drug administration route and other therapeutic parameters.3.The multifunctional nano gold imaging in vitro sensitization,radiotherapy sensitization and the fluorescence imaging in vivo validation:use a tumor-burdened mice model of building a successful intraperitoneal injection of different group of gold nanoparticles micro-after a CT scan,CT analysis lesions signal strength,clear the multi-function sensitization preoperative imaging characteristics of gold nanoparticles,evaluates the effectiveness of the nanometer gold as CT imaging contrast agent;Indocyanine green gold nanoparticles were intraperitoneally injected and irradiated with near-infrared light to evaluate the real-time fluorescence imaging effect of the multifunctional gold nanoparticles on tumor tissues in vivo.After intraperitoneal injection of different kinds of gold nanoparticles,the patients were treated with X-ray irradiation with different energy.The tumor growth curve was drawn and the survival time was analyzed to clarify the sensitization characteristics of multifunctional gold nanoparticles by radiotherapy in vivo.Research results1.Preparation of multifunctional gold nanoparticles and detection of pHysical and chemical properties:multifunctional gold nanoparticles with tumor targeting property were successfully prepared,with simple gold nanoparticles Au particle size of 20 nm.The coupling amount of glucosamine on the surface of SH-PEG-COOH labeled Au nanoparticles was 1.178 mg/mL(the concentration of Au nanoparticles was 0.1 mg/mL).The surface of SH-PEG-COOH/SH-PEG-NH2 labeled Au nanoparticles was modified with ICG-NHS and glucosamine,and the coupling amount of glucosamine was 1.328 mg/mL(the concentration of Au nanoparticles was 0.1 mg/mL).Multi-functional gold nanoparticles with particle size of about 100 nm and potential of-10 mV.TEM showed that the size of nanoparticles was uniform and the dispersion was good.NMR spectra and UV spectrophotometry showed that indocyanine green(ICG)and glucose molecules(Glu)were successfully coupled to gold nanoparticles.2.In vivo and in vitro targeted validation of endometrial cancer:the endometrial cancer cell line with high expression of glucose transporter(ISK)and the cell line with low expression of glucose transporter(RL95-2)were screened,with molecular expression levels of 35.79 and 1.61,respectively.Cell scratch assay and Transwell assay showed that ISK cells had strong invasion and migration ability.Both silenced and overexpressed glucose transporter cell lines of ISK cells were successfully constructed,and the transfection efficiency was more than 2 times.In vitro uptake of multifunctional gold nanoparticles by ISK cells with overexpression of glucose transporter protein was 4.94 times higher than that by ISK cells with silenced expression,indicating that multifunctional gold nanoparticles mediated by glucose molecules could be absorbed and internalized by multiple tumor cells.Glu-ICG-PEG-GNPs were aggregated in tumor tissues,while Glu-ICG-PEG-GNPs were aggregated in renal and liver reticuloendothelial systems.After intravenous administration,gold nanoparticles were mainly concentrated in tumor and reticuloendothelial system.3.In vivo and in vitro multifunctional gold nanoimaging sensitization,radiotherapy sensitization and in vivo fluorescence imaging verification:In vivo tumor-bearing mice were successfully constructed.Micro-CT scanning test showed that the signal intensity of gold nanoparticles group was higher than that of negative control group,and the CT imaging boundary was clear.After intraperitoneal injection,the tumor site showed obvious green fluorescence after near infrared light irradiation.In vitro radiotherapy sensitization experiment verified by MTT results showed that a large number of cells died after X-ray irradiation,while the survival rate of cells without irradiation was higher.This proves the radiotherapy killing effect of this multifunctional nanomaterial.When the concentration of gold was 4?g/mL at 72 h,the survival rates of cells were 92.34%and 68.42%,respectively,and the radiotherapy sensitization ratio was 1.35.Flow cytometry showed that under X-ray irradiation,the apoptosis rate of multi-functional gold nanoparticles was 51.13%,which was 9 times that of non-X-ray irradiation group.In vitro results showed that multi-functional gold nanoparticles increased the killing ability of tumor cells by promoting cell apoptosis.The volume of mice irradiated by intraperitoneal injection of Glu-ICG-PEG-GNPs was 329.09 mm3,while that of normal saline group was 758.12 mm3,and the tumor volume was 2.3 times that of mice irradiated by intraperitoneal injection of Glu-ICG-PEG-GNPs.ICG-PEG-Glu-GNPs,under X-ray irradiation in mice survival and longest survival shortest saline blank control group,the illuminated a tumor-burdened median surial(60 d)of mice,multifunctional nano gold radiotherapy sensitization is PBS group and no exposure of nanometer group 2.0 times and 1.2 times,proving the multi-function gold nanoparticles can significantly prolong a tumor-burdened survival time in mice.Conclusion1.The multifunctional gold nanoparticles developed in this project have the characteristics of tumor targeting,low toxicity and degradability;2.Multi-functional gold nanoparticles have biological effects of inhibiting tumor cell proliferation and invasion and promoting tumor cell apoptosis;3.Under the condition of multifunctional gold nanoparticles radiotherapy,by promoting cell apoptosis and reactive oxygen generation,the synergistic effect of the two can improve the targeted killing effect of endometrial cancer tumors;4.Multi-functional gold nanoparticles have imaging and sensitization characteristics,which is expected to achieve accurate preoperative diagnosis and accurate intraoperative resection of tumors.
Keywords/Search Tags:Cervical cancer, Endometrial cancer, Ferric oxide, Nano gold, Tumor targeting, Image sensitization, Radiotherapy sensitization
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