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Design,Synthesis And Cancer Therapy Application Of Acid-responsive Hydrogen-releasing Fe-based Nanomedicine

Posted on:2020-08-25Degree:MasterType:Thesis
Country:ChinaCandidate:Z KouFull Text:PDF
GTID:2381330623966874Subject:Materials Science and Engineering
Abstract/Summary:PDF Full Text Request
Cancer,as one of the serious threats to human health,has been the focus of research.Two of the key principles are effectiveness and biosafety.Traditional cancer treatment methods often fail to guarantee biosafety,while tumor maintenance treatments,such as gas therapy,focus on the balance between therapeutic effects and biosafety,are gradually attracting Researcher's attention.Hydrogen is the safest gas therapy molecule.but is facing a challenge that the H2 concentration at the local disease site is hardly accumulated because of its high diffusibility and low solubility,limiting the efficacy of hydrogen therapy.This paper designed a high biosafety iron-based acidic response hydrogen release drug,and the structure and properties of the material.And its tumor treatment effects and mechanisms were explored and discussed.Specifically,it can be divided into the following three parts:?1?Nano-iron particles with uniform synthetic scale,stable properties and high dispersibility.In this paper,the reduction mechanism of different dispersants?N2H4·H2O,NaBH4,AA?and the dispersion effects of different dispersants?CMC,PVP?were investigated.Finally,a uniform and stable Fe@CMC was successfully synthesized.Nanoparticles were characterized by XRD,SEM,TEM,EDS,XPS,FTIR and other materials.The results showed that the size of the nanoparticles was around150-200 nm and the iron content was 53 wt.%.?2?Based on the synthetic Fe@CMC nanomedicine,the pathway,effect and mechanism of the drug at the cellular level were explored.Experiments show that the drug has an acidic response characteristic,the fluorescent drug Fe@CMC-RBITC was successfully synthesized to verify the endocytosis of the drug at the cellular level.When the concentration reached 200?g/mL,the survival rate of different cancer cells was as low as 20%,and the normal cells were maintained at about 95%,showing high efficiency and low toxicity.This paper further explains the energy metabolism.The experiment shows that the ATP and basal metabolism of cancer cells in the drug-administered group are lower than those in the blank group,indicating that hydrogen can selectively kill cancer cells by regulating the level of mitochondrial metabolism.?3?Based on the synthetic Fe@CMC nanomedicine,explore the effect of living therapy.Experiments show that Fe@CMC has a photothermal-photoacoustic effect and exhibits good photoacoustic contrast.In the 14-day tumor-bearing mouse tumor treatment experiment,the tumor suppressive effect of the drug-administered group performed well,and the tumor volume was inhibited.About 200 mm3,the tumor volume of the blank group reached 2000 mm3 or more in the same period.The liver and kidney function tests and blood routine tests showed that the drug did not cause damage to the living body.
Keywords/Search Tags:nanomedicine, controlled release, hydrogen, tumor therapy
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