Biomedical Applications of Polymeric Nanoparticles for MR Image, Drug Delivery and Cell Detection

• Main Authors: Lin-Chen Ho, 何藺蓁
• Other Authors: Huan-Tsung Chang
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/61737289774894015061

博士 === 國立臺灣大學 === 化學研究所 === 103 === In recent years, polymeric nanoparticles (NPs) have been widely studied and developed for drug and gene carriers, medical imaging and biosensors because of their excellent biocompatibility, biodegradability. We used 1,3-phenylenediamine as a precursor to prepare nanospheres (DARs) and encapsulated with high concentration of fluorophores. The nanosphere is monodispersed, photo-stable, and the fluorescent intensity is sensitive to the pH values. The particles were characterized using super resolution microscope, and the fluorescent enhancement were tracked through single-particle technology. The mechanism called “retro-self-quench” has been established. Based on the understanding of DARs, we provide an innovative platform, termed unibody core-shell (UCS), for preparation a theranostic NPs. UCS is comprised of two covalent-bonded polymers differed only by the functional groups at the core and the shell. By conjugating Gd3+ at the stable core and encapsulating doxorubicin (Dox) at the shell in a pH-sensitive manner, we developed a theranostic NPs (UCS-Gd-Dox) that achieved a selective drug release (75% difference between pH 7.4 and 5.5) and MR imaging (r1 = 0.9 and 14.5 mM-1 s-1 at pH 7.4 and 5.5, respectively). The anti-cancer effect of UCS-Gd-Dox is significantly better than free Dox in tumor-bearing mouse models, presumably due to enhanced permeability and retention effect and pH-triggered release. To the best of our knowledge, this is the simplest approach to obtain the theranostic NPs with Gd-conjugation and Dox doping. Since the amine-rich surface of DARs are ready for functionalization, DARs loaded with Rhodamine 6G (R6GDAR) and Rhodamine 101 (R101DAR) are conjugated with aptamer sgc8c and TD05 for the detection of CCRF-CEM and Ramos cells, respectively. The concentrated fluorophores released from DARs into the cells when they taken by targeted cells, thus generate strong fluorescence and “light up” the cells. This strategy could not only rapidly recognize and quantify the target CCRF-CEM/Ramos cells with a microplate reader, but also has a remarkable detection limit as low as 80 and 221 for CCRF-CEM and Ramos cells using flow cytometry, respectively. This approach significantly simplifies the detection procedures, therefore have great potential for rapid screening.