| Summary: | 博士 === 國立臺灣科技大學 === 應用科技研究所 === 107 === Abstract
Stimuli response is a fundamental process prevalent in all living systems, where a specific function is generated in the presence of a given environmental stimulus. Engineering materials for this process is often accomplished through another basic process, self-assembly. By understanding the key aspects of these processes scientists have developed a broad range of materials for a wide array of applications. In view of the ease of fabrication, high biocompatibility, multifunctionality, and tailorable micellar properties, the development of stimuli responsive supramolecular micelle might be a promising candidate nanocarriers for controlled drug delivery and bio imaging systems. In this dissertation we have focused on three interconnected works.
In the first part, a new uracil derivative oligomer was synthesized by using aza Michael addition reaction. This newly developed stimuli-responsive nucleobase-functionalized supramolecular polymers was constructed successfully from combination of oligomeric polypropylene glycol segments as a thermosensitive group and hydrogen-bonded uracil as a photosensitive moiety. Spectroscopy analysis confirmed the successful formation of a supramolecular telechelic oligomer, where photo reactive nucleobase was attached to the ends of thermoresponsive segment. This newly designed smart material is spontaneously self-assemble in aqueous environment. Spontaneous self-assembly behavior of the material form uniform nanosized micelles via self-complementary double hydrogen bonding interactions between the uracil moieties in an aqueous environment. These micelles exhibited unique properties such as dual thermo- and photoresponsiveness, controllable lower critical concentration solution temperature (LCST), photoreactivity, and morphological transformation, making them highly attractive for various applications.
In the second part, the dissertation continued from investigation of the use of self-complementary hydrogen bonding interaction within the nucleobase functionalized smart materials to use hetero-complementary hydrogen bonding interaction in aqueous environment in order to manipulate the assembly behavior. This is a new approach which is simple but effective strategy for encapsulation and controlled drug release from supramolecular nanocarriers have been reported as a new concept in the field of drug delivery. We used adenine derivatives small molecules as a guest to integrate with the host BU-PPG self-assembled micelles via bio-complementary hydrogen bonding interactions. The host-guest complex generated have unique properties such as dual responsiveness, tunable LCST, nano-size, well defined spherical morphology and controlled release in aqueous system. In addition, photo-irradiation of the host-guest complex provides extra stability for the micelles against the serum. This finding represents a new concept that could be broadly applicable as new strategy to encapsulate and controlled release of anti-cancer drug using bio-complementary hydrogen bonding interactions as a new strategy.
In the third part, uracil-functionalized supramolecular micelles self-assembly behavior was investigated under physiological environment. The dual light- and temperature-responsive uracil-based polymer, BU-PPG was spontaneously self-assembles to form micelle-shaped nanoparticles in phosphate-buffered saline (PBS) via supramolecular interactions between uracil moieties. The resulting micelles exhibited controlled light-sensitive photodimerization, a low critical micellization concentration, low cytotoxicity towards MCF-7 cells and tunable drug-loading capacity, as well as extremely high drug-entrapment stability in media containing serum. More importantly, the drug-loaded irradiated micelles remained highly stable in serum-containing medium, and also exhibited significantly enhanced, rapid drug release in PBS at 40 °C due to the sharp hydrophilic-to-hydrophobic transition induced in the micelle structure at temperatures above the LCST. Therefore, BU-PPG offers a simple, efficient route towards the development of highly sensitive dual-responsive nanocarriers for controlled drug release, which may enable the design of safer, more efficient drug delivery systems.
Keywords: Self-assembly, temperatures, dual-responsive, nanocarriers, micelles, phosphate buffered saline, LCST, photo-dimerization, self-complementary, hetero-complementary hydrogen bonds, stability, controlled release.
|
|---|
