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Applications Of Functional Nanomaterials In The Treatment Of Diseases And Their Related Researches

Posted on:2021-03-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:K Y WangFull Text:PDF
GTID:1481306500966199Subject:Physics
Abstract/Summary:PDF Full Text Request
With the development of nanomaterials,they are applied in the treatment of diseases more and more extensively.Many functional nanomaterials have the advantages that traditional therapies lack.As the key of the drug delivery system,nanocarriers are usually able to avoid being recognized and cleared by the reticuloendothelial system,effectively prolong the circulation life of the drug in the blood,and improve the biocompatibility of the drug.Some photothermal materials have been applied to the photothermal therapies of tumors due to their intrinsic ability of photothermal conversion and low biotoxicity.They can heat up rapidly under the near-infrared laser,eventually killing the surrounding tumor cells through hyperthermia.Compared with traditional chemotherapy,this method can avoid tumor cell resistance and side effects caused by the intervention of drug.However,how to accurately and efficiently target these nanomaterials to the desired sites and perform their functions in time in order to improve the therapeutic effect of related diseases has always been a problem that researchers need to solve.In this paper,we designed a series of functional nanomaterials for improving the functions of nanomaterials in specific targeting and environmental response,hoping to further enhance the therapeutic effect of corresponding diseases and reduce side effects.The details were as follows:(1)Natural cellular membranes,with the outstanding qualities of biocompatibility and specificity,have gained growing attentions in the system of drug delivery.Nanoparticles coated with cellular membranes are starting to be applied as drug-loaded-vehicles to target tumors.Here,neutrophil membranes were selected to apply in the treatment of inflammation because neutrophils can participate in various inflammatory responses and accumulate at inflammatory sites to eliminate pathogens.Through extracting neutrophil membranes from natural neutrophils without affecting their biological properties,nanoparticles loaded with sparfloxacin(SPX)were coated with these membranes and disguised as neutrophils.Compared with traditional nano-medicines,the neutrophil membrane-coated nanoparticles(NM-NP-SPX)possessed precise targeting ability just like the neutrophils could accumulate at inflammatory sites when inflammation burst.In addition,NM-NP-SPX could prolong the circulation time and had the property of controlled-release.Through in vivo experiments,we found that the concentration of three representative inflammatory cytokines in blood,bacteria and inflammatory cells in lungs of the mice with pneumonia reduced significantly in the initial 24 h after the injection of NM-NP-SPX,which meant that NM-NP-SPX could greatly reduce the risk of death for the patients with inflammation.Moreover,the infected lungs could recover rapidly without any side effects to other organs due to the low cytotoxicity of NM-NP-SPX against normal cells.Therefore,our developed drug delivery system has enormous advantages in treating inflammations.Not only that,this kind of bionic method may have greater value and application prospects in curing the inflammations arisen from cancers.(2)In recent years,photothermal therapy induced by the near-infrared laser is being considered as a promising way to eliminate tumors due to its noninvasive nature and superior antitumor efficiency.However,the lack of ideal photothermal material impedes the further development of this new strategy.In order to break this long-standing barrier,herein we report about the copper sulfide nanoparticles(Cu S NPs)modified with polyethylene glycol(PEG)via the Diels-Alder reaction(PEG-DA-CuSNPs),a kind of semiconductor photothermal nanomaterial that possessed excellent stability and high photothermal conversion efficiency.Owing to the presence of hydrophilic PEG,the water solubility of PEG-DA-CuSNPs was significantly improved,as well as the circulation time in blood.When the nanoparticles reached the tumor tissues via the enhanced permeability and retention(EPR)effect and were irradiated by a 1064 nm laser,the local temperature increased above 90? in a short time,triggering the retro Diels-Alder reaction.PEG chains were then released from PEG-DA-CuSNPs,leading to the aggregation and enrichment of nanoparticles in the tumor,and promoting the efficacy of photothermal therapy at last.Moreover,relevant experiments also proved that our developed PEG-DA-CuSNPs exhibited low cytotoxicity to normal tissues.Therefore,we believe that PEG-DA-CuSNPs have the potential to serve as a kind of promising photothermal material in the treatment of tumor.(3)Taxol(TAX)is a typical anticancer drug that is widely used in clinical treatment of cancer,while gold nanorods(Au NRs)are a kind of well-known materials applied for photothermal therapy(PTT).To maximize the functions of TAX and Au NRs,we developed a novel multifunctional nanomaterial(LV-TAX/Au@Ag).It combined chemotherapy and PTT that were both triggered via the endogenous hydrogen peroxide(H2O2)in tumor microenvironment.LV-TAX/Au@Ag were synthesized with the artificial lipid vesicles(LV),TAX,and Au NRs that coated with silver(Au@Ag).TAX was loaded in the bilayers of LV,while Au@Ag were wrapped in the liquid core of LV.Thus,the functions of TAX and Au NRs were both inhibited temporarily.The prepared LV-TAX/Au@Ag had an average diameter of 148 nm,which made them accumulate toward the tumor tissues through the EPR effect.TAX and Au NRs were both released and their respective functions were restored after the silver shells were etched by the endogenous H2O2in tumor tissues.Under the near-infrared irradiation,extensive necrosis and apoptosis were observed in the tumor tissues and the proliferation of solid tumor was greatly suppressed due to the combined effects of TAX and Au NRs.Relevant experiments were also carried out to demonstrate the functions of computed tomography and infrared thermal imaging that were able to locate the position of tumor.In addition,no significant damage was found in normal tissues after the treatment of LV-TAX/Au@Ag.Therefore,our developed LV-TAX/Au@Ag can treat cancer accurately and efficiently without any side effects,indicating the great promise and value for future cancer therapy.
Keywords/Search Tags:functional nanomaterial, inflammation, neutrophil membrane, tumor, copper sulfide nanoparticles, photothermal therapy, gold nanorods, combination therapy
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