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        우타만 사지 전남대학교 2016 국내박사

        RANK : 232223

        Today, nanotechnology plays a vital role in biomedical applications, especially for the diagnosis and treatment of various diseases. Particles in the size range of 10 to 1000 nanometers are usually termed as nanoparticles. They have attracted much interest in recent years as ideal candidates for various biomedical applications such as drug delivery systems and bio imaging, owing to their specific properties of size tunability and intrinsic hydrophilic surfaces. They are generally classified as either natural polymer-based, synthetic polymer-based and metallic based nanoparticles. Natural polymer-based nanoparticles are considered better candidates for drug delivery than synthetic polymer-based nanoparticles. In our first study, a new type of targeted bacteriobots was proposed as the therapeutic strategy for anticancer therapy against solid tumors. A maleimide-functionalized hyaluronic acid (HA) polymer was synthesized, and then cross-linked with 4-arm thiolated polyethylene glycol (PEG) to form HA microbeads with a diameter of 8 µm through Michael-type addition. Docetaxel-loaded nanoparticles were encapsulated into HA-PEG microbeads for the therapeutic purpose. In vitro drug release profile of the DTX from HA-PEG microbeads exhibited sustained drug release pattern for a long period up to 96 hrs. Fabrication of dual targeted bacteriobots were done by the formation of CD 44 targeting HA microbeads via microfluidics, followed by the attachment of the flagellar bacteria Salmonella typhimurium genetically engineered for tumor targeting onto the surface of the HA microbeads by the specific interaction between streptavidin on HA beads and biotin on bacteria. After attachment of bacteria onto the surface of HA microbeads, the bacteriobots showed a velocity of0.72 µm/s. In addition, the bacteriobots showed high chemotactic migration velocityof 0.43 µm/s towards 4T1 cells lysates.CD 44 specific cellular uptakes were verified through flow cytometry analysis and confocal imaging, demonstrating enhanced intracellular uptake in CD 44 positive tumor cells compared to normal cells. Therefore, the present study suggested these bacteriobots have dual tumor targeting abilities and also proved that they can be considered as an excellent candidate for targeted anticancer therapy. In our second study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI.

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