Design, Synthesis, and Characterization of SupramolecularNanobeacons for Cathepsin B Detection

nanobeacons;cathepsin B;Chemical & Biomolecular Engineering

Reyes, Claudia D.

Johns Hopkins University

关键词: nanobeacons;    cathepsin B;    Chemical & Biomolecular Engineering;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/37087/REYES-THESIS-2014.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Cancer imaging is vital for various applications in cancer treatment and research because it has the potential to overcome challenges within these fields. Surgical removal of tumors is limited by the inability to clearly assess tumor margins, but imaging can aid in the visualization of these margins. Cancer imaging can also help researchers see, monitor, and analyze the therapeutic effects of developed therapies on cancer cells. Currently, nanotechnology is being implemented into cancer imaging due to the potential to create nanoparticles designed to target cancer cells, improving the effectiveness and sensitivity of cancer imaging. In this study, two types of supramolecular nanobeacons, SFB-K and SFB-E, were designed and synthesized to detect the cancer protease, cathepsin B, for cancer imaging. The nanobeacons were characterized by performing three different studies that determined how their self-assembly and cellular uptake were affected by different components. Nanobeacon self-assembly was studied by analyzing Transition Electron Microscopy (TEM) and circular dichroism (CD) time-course data of samples with different nanobeacon concentrations and kinetic pathways. These two studies showed that higher concentration and pre-existing structures induced the self-assembly of the nanobeacons from spherical to cylindrical nanostructures. The effect of surface charge and shape on nanobeacon cellular uptake was also analyzed by using flow cytometry to measure the cellular internalization of three sets of nanobeacons samples, SFB-K, SFB-E and SFB-KE, with different surface charges and shapes. The results from this study concluded that there is an interdependent relationship between nanobeacon surface charge and shape with cationic spherical nanobeacons having the highest internalization rates. The data from these studies demonstrate how the properties of supramolecular nanobeacons can be tuned to optimize their performance. By defining some of the properties needed to reach optimal performance, future research with the SFB series nanobeacons involves the loading of a chemotherapy drug, such doxorubicin, onto the nanobeacons for more specific and effective drug delivery to cancer cells.