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Multi-functional Materials For Targeting Tumor Theranoastic

Posted on:2018-07-02Degree:MasterType:Thesis
Country:ChinaCandidate:S P LiFull Text:PDF
GTID:2334330566455732Subject:Materials engineering
Abstract/Summary:PDF Full Text Request
Nowdays,cancer is seriously threatening human health at high increasing speed among people.We need more accurate technologies to fight against tumor immediately.In order to obtain better treatment effect,the theranostics that integrate imaging and therapy functionalities have been attracting more attention in cancer treatment.At the treatment methods,there are many new technologies,such as,photothermal therapy,photodynamics therapy and immunization therapy.Meanwhile,the multi-modal imaging technologies are getting improved for more precise diagnosis in cancer.At this condition,the multi-function targeting material plays a vital role and has preponderances in reducing the toxicity of anticarcinogen or realizing synergistic treatment.With the advantages of below materials,I design two experiments.At first,hyaluronic acid(HA),a natural polysaccharide,have been constructed into nanoparticles which can bring drugs into the tumor with high efficiency successfully due to passive(EPR effect)and active(over-expressed receptor CD44 of HA on the tumor)targeting.The nanoparticle shows ability of rapidly uptake into cancer cells via HA-induced endocytosis mechanism.What's more,HA were high biocompatibility and biosafety in vivo.Secondly,Near-infrared(760-1000 nm)heptamethine cyanine have been used for optical therapy and imaging in cancer due to their excellent fluorescent properties in the NIR region in which biological tissues have weak light absorption and lights have deep tissue penetration.At same time,they also can be used to cure cancer as photosensitizer,such as,ICG approved by FDA.Continually,some of them(IR780,IR808)have targeting ability to tumor cell.With the advantages of HA and cyanine dye,the multi-functional targeting materials can be made to realize better the therapeutic efficiency in optical/photoacoustic targeted dual-modal imaging-guided cancer therapy.1,Developing heptamethine cyanine-conjugated hyaluronic acid nanoparticles for optical/photoacoustic targeted dual-modal imaging-guided cancer photothermal therapyAt first,HA was grafted with ADH.Then,the IR808 was connected with HA via hydrazone bond.The HAIR nanoparticle was formed by self-assembly of hyaluronic acid-grafted cyanine dye IR808 molecular in the water solution.The average diameter of particle was 125 nm and the shapes of them were almost spherical.The HAIR nanoparticles not only have good fluorescence imaging,but also apparently improved the stability of fluorescence.The Cy dyes under a laser can be easily oxidated by ROS that largly reduce the availability of them in treating cancer.Furthermore,the nanoparticles apparently improved the stability of fluorescence and largely enhanced the photo-thermal conversion efficiency of IR808.In vitro,the tempareture of HAIR nanoparticles would rise to 55 ?,while,the tempareture of free IR808 was only rising a little bit.At same time,the intensity of acoustic signal in HAIR NPs is higher than free IR808.In addition,the HAIR NPs were injected intravenously into tumor-bearing mice to demonstrate the therapeutic efficacy of PTT guided by NIRF/PA dual-imaging.The experimental results demonstrated that HAIR NPs were nanoplatfrom with high biocompatibility,biosafety and therapeutic effect.Therefore,the HAIR NPs have a novel potential for fluorescent/photoacoustic targeted dual-modal imaging-guided cancer photothermal therapy.2,GSH responsive molecule,cyanine connecting MTX for cancer theranostic targeted dual-modal imaging-guided cancer phototherapy and chemotherapy.Hererin,the new single molecular Cy-SS-MTX was constructed by conjugating IR780 having targeting tumor ability and MTX also having a little bit with cystamine.For one thing,the molucler IR780 bring the MTX to tumor effectively.The intracellular GSH can open the disulfide bond between IR780 and MTX.Thus,the cancer can be treated by chemotherapy of MTX and photothermal therapy of IR780.In addition,the molecular system also provides dual-modal imaging(fluorescence and photoacoustic imaging).Then,the uptake and toxicity in cancer cells were measured.From the result,the IR780 improved the uptake and reduced the resistance of cells to MTX.Thus,the single molecule Cy-SS-MTX can improve treatment effcct of MTX to tumor.In the end,the molecule system,Cy-SS/CC-MTX would reach the tumor early than IR780 analyzed from fluorescence imaging in mice.The dual-targeting tumor of materials might cause that phenomenon.Furthermore,under the two kinds of excitation wavelength(640 nm,745 nm)in the tumor,we could directly measure the trend that the fluorescence intensity(excitated in 745 nm)gradually increased.That apparently account for the disulfide bond which be opened by GSH in the cell.Overall,this novel molecule can be helpful in the diagnosis of cancer and provide a new way for targeting imaging and therapy.
Keywords/Search Tags:Multi-functional targeting material, theranostic, hyaluronic acid, heptamethine cyanine, MTX
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