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Light-Triggered Nanoparticles As Tumor-Specific Theranostics Carrier

Posted on:2018-05-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:B WanFull Text:PDF
GTID:1314330515483370Subject:Medical imaging and nuclear medicine
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Early diagnosis and proper disease management of tumor,as well as the personalized medicine and therapy monitoring,depend on the precise diagnosis of tumor.Since CT,MRI,and optical imaging all have their own strengths and weaknesses,the combination of these imaging techniques are more preferable for comprehensive and precise information of patient.The CT/MRI imaging signal can be modulated with contrast agents(CAs)by absorbing X ray or shortening the relaxation time of water protons to improve the visibility.In order to improve the target ability,selectivity and modest signal/noise ratio of CAs in cancerous tissues,arrange of stimuli has been employed to develop stimuli-responsive release system.Recently,light induced release systems of drugs o?ering on-demand targeting capability provide new unique opportunity for image-guided therapies.The use of light to generate heat has been proven to improve specific release and cellular uptake for theranostics agents.Porphyrin and its derivatives have attracted particular attention in cancer diagnosis and treatment,and been FDA-approved photosensitizer due to its preferential uptake by tumor cells and attractive photo-physical properties in photodynamic therapy(PDT).Porphyrins have been widely used as a chelate due to its intrinsic ability to chelate various of metal ions.Meanwhile,researchs have developed several metalloporphyrins as MRI contrast agents and reached good contrast enhancement.By the combination of chemotherapy drugs and metalloporphyrin chelate,it can reduce the side effects of chemotherapy while preserving the PDT and imaging contrast.Based on these problems,we disign and synthesis two light-trigger response tumor-specific imaging and therapy nanostructures LTCAs and Gd-Pt-Porphyrins.1 In this work,LTCAs was fabricated via self-assembly method.The LTCAs were comprised of three components:a hydrophilic core,a thermo-responsive phospholipid bilayer(DPPC/DSPC)and a hydrophilic polyethylene glycol(PEG)shell.As expected,iohexol,magnevist,and IR820 were successfully entrapped into the core of LTCAs.NH4HCO3,that could generate CO2 bubbles when illumined by near infrared(NIR)light,was also encapsulated in the lipid.Transmission electron microscopy imaging showed that LTCAs have good water solubility,dispersion and stability.Firstly,cell toxicity experiment indicated the well biocompatibility of LTCAs.Then,in vivo MRI/FI imaging after laser irradiation showed more effective contrast enhancement triggered by NIR laser compared with the control group without irradiation.Additionally,due to the high photothermal conversion efficiency of IR820,the injection of LTCAs was demonstrated to completely inhibit C6 tumor growth in nude mice up to 17 days after NIR laser irradiation.2 In this work,we innovative conjugate the cisplatin and Gd(?)to tetraplatinated porphyrin and synthesis of theranostic tetraplatinated porphyrin complexes(Gd-Pt-Porphyrins)for MRI-guided cancer photodynamic therapy and chemotherapy.Gd-Pt-Porphyrins has low cytotoxicity and good biocompatibility.HeLa cell can uptake porphyrin or its derivatives and accumulate in the nucleus.Gd-Pt-Porphyrins displayed a pronounced light-mediated cytotoxicity towards HeLa cell lines and C6 glioma bearing nude mice upon irradiation.In addition,the longitudinal relaxivity of Gd-Pt-Porphyrins is about two-fold compared to the clinically used Magnevist,and the injection of Gd-Pt-Porphyrins showed effective MRI contrast enhancement in vivo.
Keywords/Search Tags:light-triggered, near infrared light, porphyrins, tumor-specific, multimodal imaging, photothermal therapy, photodynamic therapy
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