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Application Of Self-assembled Short Peptides In Drug Delivery

Posted on:2020-06-29Degree:MasterType:Thesis
Country:ChinaCandidate:M YeFull Text:PDF
GTID:2381330575489648Subject:Pharmaceutical
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The supramolecular discipline based on molecular self-assembly is a frontier subject that has received much attention in recent years,and self-assembled short peptides are an important component of self-assembled molecules due to their good biocompatibility,biological activity,and easy modification.And many other advantages have become hot research subjects in the fields of tissue engineering,cancer treatment and drug delivery.Self-assembling short peptides can form functional nanostructures with specific ordering through non-covalent interactions.These nanostructures are widely used for drug delivery due to their good drug loading capacity and high environmental responsiveness.The application in drug delivery is mainly based on two methods,namely self-assembling short peptide encapsulation drugs to achieve drug storage,drug retention and therapeutic effects;and covalent combination of drug molecules and self-assembled short peptides as a part of the whole.Based on this,we conducted the following two parts based on drug delivery studies1.Gene therapy,as a potential and effective method for treating human genetic diseases,has received great attention in the past few decades.However,oligonucleotides and plasmid DNA used for gene therapy cannot be effectively absorbed by cells due to their size,charge and stability,which seriously affects their efficacy.In this paper,we use self-assembled short peptides as a vector for gene delivery,physically encapsulating plasmid DNA in the assembly,thereby realizing the delivery of self-assembled short peptides to plasmid DNA.We designed and synthesized Nap-GFFHHHHHHYIGSR-NH2polypeptideusingpeptide self-assembly technology.In this sequence,HHHHHH can show high endosomal escape ability due to proton sponge effect;YIGSR can target cell membrane upper laminin receptor and increase cell uptake rate;and peptide and plasmid DNA can be combined by self-assembly to reduce plasmid DNA Negative charge exposure overcomes several obstacles in gene transfection,including endosomal escape,cell targeting,and charge effects.Our peptide self-assembly gene transfection vector has the advantages of low toxicity and safety,and it is expected to provide an excellent choice for gene therapy vectors.2.Myocardial tissue is inevitably damaged during cardiac ischemia-reperfusion.We chemically bind the therapeutic drugs telmisartan and angiotensin 1-7(Ang1-7)to the polypeptide to form a new one.The assembly of the compound to achieve self-assembled short peptides for the delivery of therapeutic drugs has the greatest advantage of being able to overcome the short-lived defects of Ang1-7,achieve sustained release of the drug and exert synergistic therapeutic effects.Our study provides a promising option for drug combination therapy for cardiac ischemia-reperfusion.
Keywords/Search Tags:Self-assembling short peptides, Nanomaterials, Drug delivery, Gene transfection, Synergistic treatment
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