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Construction Of Biomimetic Fluorescent Liposome Probe And Its Application In Imaging And Treatment Of Hepatic Alveolar Hydatid

Posted on:2024-11-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:X X XiongFull Text:PDF
GTID:1524307355988639Subject:Medical imaging and nuclear medicine
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Purpose: Leveraging the inflammatory chemotaxis capability of neutrophils,we have successfully engineered a nanoprobe named Neu-Lipo-ICG by extracting the membrane of neutrophils from mice and modifying it with indocyanine green(ICG)liposomes.Firstly,this investigation sought to establish a foundation by constructing a hydatid cyst-infected gerbil model,aiming to simulate the characteristics of human hydatid disease.In the murine model of hydatid cyst infection,the authors conducted an assessment of the inflammatory targeting capability of Neu-Lipo-ICG,accomplishing successful near-infrared fluorescence imaging of hydatid cyst lesions.The application of this technology offers a novel avenue for the early diagnosis of hydatid disease.Through the enhancement of inflammatory targeting capabilities,precise localization of the infected focus becomes achievable,providing an effective means for the early detection of lesions.Furthermore,building upon the photothermal properties of Neu-Lipo-ICG,the researchers innovatively established a photothermal ablation method for hydatid disease in experimental settings.The successful elimination of the infection focus through photothermal therapy introduces a new perspective forminimally invasive treatment of hydatid disease.This integrated approach of fluorescence diagnosis and photothermal therapy not only enhances the precision and effectiveness of treatment but also reduces invasiveness for patients,bringing newfound hope to the treatment of hydatid disease.In summary,this study comprehensively utilized the characteristics of neutrophils,successfully developing the Neu-Lipo-ICG nanoprobe and validating its outstanding performance in inflammatory targeting and photothermal therapy within the hydatid disease model.This breakthrough offers entirely new technologies and methods for the early diagnosis and treatment of hydatid disease,showcasing significant clinical application prospects.Methodology: In this research endeavor,we employed the thin-film hydration technique to fabricate liposomes encapsulating indocyanine green(ICG).Through the meticulous application of physical extrusion,we achieved the successful integration of the membrane from neutrophils – a structure akin to the bilayer of liposomal phospholipids – onto the surface of ICG liposomes.This intricate process gave rise to the creation of a nanoprobe,elegantly named Neu-Lipo-ICG.This method artfully amalgamates nanotechnology with the structural intricacies of biological membranes,laying a robust foundation for subsequent investigations.Subsequently,we delved into an in-depth exploration of the targeted imaging capabilities of Neu-Lipo-ICG in the inflamed regions of the livers of gerbils infected with hydatid cysts,utilizing in vivo near-infrared fluorescence imaging technology.In comparison with conventional ICG liposomes,our meticulous analysis,combined with ex vivo near-infrared imaging,thoroughly substantiated the exceptional targeting prowess of Neu-Lipo-ICG.This pivotal step not only ensured the precise localization of Neu-Lipo-ICG in inflammatory sites but also provided a reliable basis for subsequent therapeutic experiments.Building upon the foundation of Neu-Lipo-ICG’s targeted imaging,we further investigated its photothermal effects.By subjecting Neu-Lipo-ICG to continuous-wave near-infrared laser irradiation at 808 nm,we successfully triggered its photothermal response.Recording the changes in thermal elevation in the hepatic region of gerbil models using a near-infrared imaging system,we elucidated the deleterious effects of Neu-Lipo-ICG-mediated photothermal therapy on hydatid cysts.This innovative therapeutic approach paves the way forminimally invasive treatments of hydatid disease.Lastly,we conducted ex vivo pathological analyses to confirm the therapeutic effects of Neu-Lipo-ICG-mediated photothermal therapy.This comprehensive research design not only achieved significant breakthroughs in technological methodologies but also provided novel theoretical and practical support for the treatment of hydatid disease,offering considerable prospects for clinical applications.Results: In the course of our investigation,we adeptly employed the thin-film hydration technique to successfully fabricate liposomes encapsulating indocyanine green(ICG).Through the sophisticated application of physical extrusion,we achieved the successful integration of the neutrophil membrane onto the surface of ICG liposomes,forming a nanoprobed structure with a spherical configuration,gracefully named Neu-Lipo-ICG.Possessing dimensions on a larger scale,approximately 120 nm,it exhibited superior fluorescence characteristics.The ICG molecules exhibited robust near-infrared absorption at 780 nm,with a fluorescence emission peak at 810 nm.Under the radiant exposure of an 808 nm laser,Neu-Lipo-ICG demonstrated commendable photothermal performance,elevating the temperature to 45℃ in a mere 10 minutes.Furthermore,its photothermal capabilities displayed a positive correlation with concentration and laser power.Experimental validation in a murine model of hydatid cyst infection confirmed the successful targeting of hepatic lesions by Neu-Lipo-ICG,accompanied by a vivid near-infrared fluorescence display.Quantitative results revealed that,24 hours post-injection,the fluorescence signal in the Neu-Lipo-ICG group surpassed that of the Lipo-ICG treatment group by a factor of 4.2.In intravenously administered mice receiving Neu-Lipo-ICG,the temperature in the hepatic region rapidly increased by 15.4℃ within the initial 3 minutes under near-infrared laser irradiation,subsequently stabilizing at 46.7℃.Over the 7-day monitoring period,Neu-Lipo-ICG-mediated photothermal therapy significantly reduced lesion volume,validating its effective eradication of hydatid cysts under near-infrared laser exposure.It is noteworthy that neither standalone laser irradiation nor exclusive administration without irradiation in the control groups exhibited any inhibitory effects on hydatid cyst infection.These research findings comprehensively affirm the prowess of Neu-Lipo-ICG as a highly biocompatible and efficient photothermal agent,demonstrating potential advantages in treating hydatid disease.The synergistic interplay of its targeting capabilities and photothermal effects heralds a new paradigm for hydatid disease treatment,promising vast applications.By seamlessly integrating nanotechnology and biological membrane structures,we have not only heightened therapeutic efficacy but also provided insightful guidance for future research in photothermal therapy.This innovative exploration opens new avenues for the treatment of hydatid disease,furnishing robust support for related fields of inquiry.Conclusion: The findings of this study underscore the tremendous potential of the developed Neu-lipo-ICG in near-infrared fluorescence-guided photothermal therapy,presenting a new vista for the treatment of hydatid disease.We conducted a comprehensive and profound investigation into the optical and photothermal performance of Neu-lipo-ICG,affirming its ideal application in the realm of photo-therapeutic diagnostics.In comparison to the conventional Lipo-ICG,the hydrophilic membrane coating technique employed imparts Neu-lipo-ICG with a unique chemotactic effect,showcasing distinctive specificity in targeting hydatid-infected tissues and providing a more precise localization for treatment.In the murine model of echinococcosis infection,Neu-lipo-ICG exhibited a prolonged residence time,and,when contrasted with the Lipo-ICG treatment group,manifested a significantly augmented active targeting capability.This outcome accentuates the in vivo distribution and targeting performance of Neu-lipo-ICG,robustly supporting its feasibility in practical therapeutic applications.Simultaneously,our in vitro and in vivo studies indicate that Neu-lipo-ICG holds potential for sensitive diagnosis and effective treatment of cystic echinococcosis in murine models.This opens new avenues for future clinical treatments,furnishing more efficient and precise therapeutic means for patients with hydatid disease.It is noteworthy that this study marks the pioneering attempt to employ biomimetic liposomes for the prospective diagnosis and treatment of zoonotic diseases.The successful application of Neu-lipo-ICG paves the way for a novel and efficient approach to tackling infectious diseases in underdeveloped regions,not only innovating therapeutic modalities but also providing a notable case in the application of nanomedicine in the field of zoonotic diseases.In this study,we have vividly showcased the potential applications of functional nanomaterials,laying a solid foundation for future research in related fields.
Keywords/Search Tags:Hydatidosis, Biomimetic Cell Membrane, Indocyanine Green, Near-Infrared Fluorescence Imaging, Photothermal Therapy
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