The Preparation Of Multifunctional Targeting Nanoplatform And Its Application In The Treatment Of Liver Cancer

The high incidence and death rate of liver cancer makes it a threat to human life and leads to health.Generally,the properties of liver cancer is relatively hidden,the incubation period is longer,and the tumor growth rate is rapid,which leads to the difficulty in diagnosis of liver cancer.In the clinical treatment of liver cancer,surgical resection is first considered,and comprehensive treatment is carried out by chemotherapy,radiotherapy,etc.To a certain extent,the therapeutic effect is improved by using the above methods,but the long-term survival rate of patients of liver cancer is still low.Once the presence of multidrug resistance,recurrence and metastasis of the tumor,the cause hopeless of the further treatment.Therefore,the early diagnosis and early treatment of liver cancer has become an important factor in the prognosis of patients,improve the quality of life,but still can not overcome the above situation.In order to solve the problem of drug resistance,improve the curative effect and reduce the side effects,it is a hot issues of research and a challenge in the treatment of cancer.With the improvement of science and technology,the emergence of nanomedicine has brought new opportunities for the diagnosis and treatment of malignant tumors.Functional nanomaterial,both in the imaging and diagnosis,as well as the carrier for the construction of nanodrug,even in the diagnosis and treatment of multifunctional nanoplatform development,has emerged as the sensitivity and accuracy of diagnosis,which can improve and overcome the resistance of cancer and improve the curative effect and other excellent properties.And It can also to further reduce the drug randomly dispersed causing the side effects.It shows a great prospect in clinical application.In recent years,in the field of targeted drugs,visualization of surgical navigation,image-guided treatment,have made considerable progress and laid an important foundation for personalized precision medical strategy.The application of nanomaterials and technology in this doctoral thesis,aiming at the existing problems in the treatment of liver cancer,focusing on drug resistance and randomly dispersed chemotherapy drugs,combined with molecular imaging methods to carry out early diagnosis and treatment of liver cancer.Specifically as follows:(1)In this study,It is mainly aimed at the difficulties of the early diagnosis and treatment of liver cancer in clinical,such as the traditional chemotherapy toxicity,and the poor effect,the emergence of drug resistance.Based on the advantages of targeting nanosystem in tumor therapy,a new method of visualization diagnosis and treatment of liver cancer was proposed.The copolymer modified with Lactobionic Acid(LA)to target to the high affinity of Hep G2 cell membrane surface Asialoglycoprotein Receptor(ASGP-R)and mixed with TPGS,which is an inhibitor of P-gp protein as drug carriers;and iron oxide nanoparticles as MRI imaging agent.The surface of LA will make the nanoplatform selectively targeted to Hep G2 cells,this is the first level of drug targeting;the targeted deliver of drug to two subcellular organelles of nuclei and mitochondria in the transportation as the next step of target,the above strategy will improve the antitumor activity and reversal of drug resistance.In addition,with the help of MRI imaging reagents,the real-time monitoring of tumor drug accumulation,distribution in tumor,and drug release dynamics will be an important step to practice the precision medicine.in the early stage.(2)The stimuli-responsive smart strategy of near infrared image-guided therapy and its application in the diagnosis and treatment of liver cancer.According to the properties of acidic condition of tumor microenvironment and high concentration of GSH in tumor cells,the drug-loaded mixed micelles with p H and redox were constructed.At the same time,combined with NIR dye of IR806 in the mixed micelles,it has the advantage of deep tissue penetration depth and no background fluorescence.It can be used to detect the drug-loaded mixed micelles accurately,to observe the drug delivery in real time and to monitor the distribution of drugs in the tumor.In particular,the IR806 molecule is attached to the hydrophobic end of the copolymer,which avoids the problem of the decrease of the imaging accuracy,caused by the leakage of the dye.The results of this study showed good antitumor activity in response to drug delivery strategies in liver cancer.A new method for the integration of diagnosis and treatment of liver cancer is provided,which provides an important step for the early visualization of liver cancer therapy.