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Stdudy On Immunological Characteristics Of Nanomaterials And Combination Cancer Immunotheropy Of OVA-HBc NCs And Chemotherapeutic Drugs

Posted on:2020-05-04Degree:MasterType:Thesis
Country:ChinaCandidate:H P ZhengFull Text:PDF
GTID:2404330572482522Subject:Biology
Abstract/Summary:PDF Full Text Request
Biological nanomaterials are widely used in medical research because of their unique advantages.In recent years,the role of nanoparticles in inducing immune re-sponse has attracted much attention.However,it is still in the exploring stage of expe-rience and lacks the corresponding theoretical guidance.The differences and similari-ties of immune responses induced by different nanomaterials need to be further sum-marized.The biosafety of nanomaterials still needs further study.Based on this,several common inorganic nanoparticles(including Au NPs,Au-Rod NPs and Fe3O4 NPs)usu-ally used in nanomedicine research were selected as the research objects.The recogni-tion,activation and response of immune system after immunization with nanomaterials were explored through traditional immunology methods,and these nanomaterials were systematically evaluated the differences and similarities in inducing immune responses.Our results show that Au NPs can significantly improve the ability of antigen to stimu-late dendritic cells maturation.Au NPs mixed with the antigen protein injection were easier to migrate and enrich in the draining lymph nodes of mice,improve the prolifer-ation of antigen-specific T cells in lymph nodes and promote immune response.In ad-dition,through the comparative analysis of enhanced T cell activation by different in-organic nanoparticles(including Au NPs,Au-Rod NPs and Fe3O4 NPs),we found that Au-Rod NPs could better induce T cell activation.All the three materials can enhance the differentiation of Th1 cells,but the effect of Au-Rod NPs is the most obvious.The most surprising finding is that Au NPs and Fe3O4 NPs could induce stronger differenti-ation of Treg cells,while Au-Rod NPs could partially inhibit the differentiation of Treg cells.This suggests that Au-Rod NPs may be more suitable for anti-tumor immunity than Au NPs and Fe3O4 NPs.The results have important guiding significance for the rational application of nanomaterials.In addition,based on the results of previous stud-ies,we further studied the application of the constructed nano-tumor vaccine OVA-HBc NCs in the combined treatment of tumors.Our results showed that OVA-HBc NCs,as a therapeutic vaccine,significantly increased the number of OVA antigen-specific toxicT cells and significantly decreased the number of Treg cells in mice after combined with low-dose paclitaxel treatment compared with the single treatment group,which can effectively inhibit the lung metastasis of B16-OVA-Luc tumor cells.At the same time,we found that the number of memory T cells(TCM,central memory T cells;TEM,effective memory T cell)of mice treated with OVA-HBc NCs combined with low-dose paclitaxel increased significantly,and the survival time of mice prolonged.Our study-provides a new idea and strategy for nanoparticle-based tumor immunotherapy.
Keywords/Search Tags:Nanomaterials, Hepatitis B core protein, Cancer immunotherapy
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