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Targeted Drug Delivery And Detection Application Research With Lysosomal Escape Function

Posted on:2021-02-18Degree:MasterType:Thesis
Country:ChinaCandidate:Y H HuFull Text:PDF
GTID:2431330605463913Subject:Analytical Chemistry
Abstract/Summary:PDF Full Text Request
In recent years,we have found that nanotechnology has received widespread attention in the diagnosis and treatment of diseases,and nano-drug delivery systems,nano-probes,etc.have been continuously developed and utilized.Among them,endosome / lysosomal escape technology has played a significant role in promoting the development and application of nano-systems in the diagnosis and treatment of diseases due to its unique solubilizing properties.It is widely used in life imaging and detection and targeted treatment of major diseases.Based on this,we designed and synthesized a tumor treatment strategy and a tumor diagnosis strategy.The specific research contents are as follows:1.Construction of multidrug delivery system based on endosomal escape technology and small molecule peptide self-assembly technology: First,non-toxic DNPs formed by dipeptide selfassembly have safety and biocompatibility.Second,from the perspective of multifunctional nanoparticles for nanomedicine tumor imaging surveillance,AS1411 and HA are used to enhance drug targeted delivery and improve endosome escape,respectively.Third,from the perspective of effect,the synergistic effect of Clolar,siRNA and DOX improved the inhibitory effect.Cell experiments and in vivo experiments have shown that multi-drug synergy therapy is superior to single-drug therapy.Therefore,dipeptide nanoparticles / clofarabin / Aptamer AS1411 / flu hemagglutinin peptide / siRNA / doxorubicin(DNPs / Clarar / AS1411 / HA / RNA / DOX)multifunctional nanoparticles are used for specific delivery,Cancer treatment and biological imaging.It is an ideal choice for multi-drug synergistic therapy,and proposes new ideas for these hybrid anti-cancer drugs.2.Construction of GSH fluorescent probes based on endosomal escape technology and AIE luminescence mechanism: According to the advanced characteristics of AIE fluorophores widely used in the field of biosensing and bioimaging(such as superabsorption,high luminosity and high whitening resistance).We selected streptavidin-modified magnetic beads as the carrier,and modified a unique aggregation-induced emission(AIE)fluorophore TPE on the outer layer of the magnetic beads with biotin-modified DNA.At the same time,we modified the magnetic beads with biotin-modified influenza virus hemagglutinin peptide(HA),so that the resulting nanoprobe can enter more cells.Under the action of GSH,a click reaction is used for detection.This provides a new idea for the quantitative analysis of the tumor marker GSH.In short,this article based on endosome / lysosome escape technology,combined with the targeting of nucleic acid aptamers and the unique advantages of nanomaterials,has done research on targeted diagnosis and treatment of tumors,which will be used for future research on tumor diagnosis and treatment.Provides theoretical basis.
Keywords/Search Tags:Endosomal/lysosomal escape, Targeting vector, Tumor diagnosis and treatment, Aggregation-induced luminescence, RNA, DNA
PDF Full Text Request
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