| China has high prevalence with viral hepatitis,an estimated 93 million people are living with hepatitis b3 and tiiere are 0.3 million new liver cancer each year,liver cancer is the second leading cause of cancer mortality worldwide,Early diagnosis and surgery is thus far the most efficient treatment for HCC.As the condition is insidious and advances gradually,the disease is diagnosed only after the patients have severe liver cirrhosis or distant metastasis,which loss the opportunities of radical surgery for the early stage,chemotherapy is the main treatment method for medium-term or advanced HCC,however,chemotherapy agents are weak selectivity,and the chemotherapy drugs will cause injury to normal tissue cells in varying degrees while it make effects ontumor cells,resulting in big side effect etc.in recent years,drug delivery system is emerging as a feasible chemotherapy choice.By using polymer materials,it could release therapeutic molecules in the diseased tissues in the form of physical absorptionor encapsulated small molecular drugs,and therefore make full use of medicinefs curative effect* Nano drug microspheres is expected to replace traditional drug dosage with non-toxic,targeted delivery and controllable slow release,effectively reduce the dosage of chemotherapy drugs,enhance the accumulation of drug in the tumor site,greatly improve the efficiency of drug,enhance curative effect and reduce the adverse reaction of normal tissue.The unique advantages of nano drug make it has the broad prospects for development and clinical application value,therefore,developing a new type of nanomedicine with high anti-tumor activity,and study its curative efifect and mechanism further will effectively improve the survival rates of liver cancer patients,and provide a new strategy for comprehensive treatment of liver cancer" Molecularly targeted agents that are designed to target specific lesions have been proven effective as clinical cancer therapies;however,most currently available agents are poorly water-soluble and require oral administration,thereby resulting in low bioavailability and a high risk of side effects due to dose intensification.The rational engineering of systemically injectable medicines that encapsulate such therapeutic payloads may revolutionize anticancer therapies and remains an under-explored area of drug development.In this study,we use the polymer to preparation vandetanib loaded nanomedicine and study the anti-tumor activity of NP-vandetanib in vivo by intravenous administration.PEG-PLA was used to coassemble with this potent agent to form water-soluble NPs.electron microscope,DLS and in vitro drug release experiments were used to characterize the surface chemical properties and release properties.And then,the effects of NP-vandetanib on cell proliferation,cell apoptosis,HUVECs invasion and migration ability and angiogenesis were detected using cell counting kit-8(CCK8)assay,Flow cytometry apoptosis assay,Flow cytometry cell cycle assay,transwell invasion and migration assay,neovascularization.Furthermore,we investigated the in vivo anti-tumor efficiency of NP-vandetanib in subcutaneous transplanted model of human HCC in nude mice.The results suggested that NP-vanib could effectively inhibited human hepatoma cells proliferation and tube formation,metastasis,and angiogenesis of HUVECs.The intravenously injection of NP-vanib into mice bearing HCC BEL-7402 xenografts more effectively inhibited the tumor than the oral administration of vanib.In addition,due to the modular design of these NPs? the drug-loaded particles can easily be decorated with iRGD,a tumor-homing and tumor-penetrating peptide,which further improved the in vivo performance of thesevanib-loaded NPs.Our results demonstrate that reformulating targeted therapeutic agents in NPs permits their systemic administration and thus significantly improves thepotency of currently available,orally-delivered agents.. |
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