| Summary: | 博士 === 國立交通大學 === 材料科學與工程學系奈米科技碩博士班 === 107 === In this dissertation, we have attempted to develop a series of single and two component hydrogels based on ultrashort aromatic peptide amphiphiles and evaluate their applications. This thesis is composed of 8 chapters, the first chapter deals with the general introduction. The second chapter describes the materials and methods that are used for synthesizing and characterizing the hydrogels. Chapter-3 and 4 describe design synthesis and hydrogelation of a series of peptide amphiphiles capped with naphthalene diimide (NDI) and pyrene chromophores. In chapter-3 NDI conjugated single amino acid and pyrene butyric acid (Py), were used to promote the formation of the supramolecular nanofibers and Charge transfer (CT) hydrogels. Amino acid sequences were found to have significant influence on the structural morphology and stability of the hydrogels. In chaper-4, the supramolecular hydrogelation of NDI-Py mixed component systems were described. Such system provided opportunities to construct new type of supramolecular hydrogels through aromatic complementary CT
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interactions. In addition NDI and Pyrene based single amino acids with a match pair and mismatch pair giving a stable hydrogel of nanofibrous morphology with the average diameter of about 6-9 nm as evidenced by TEM analysis. In addition, this novel NDI-Py mixed component system exhibited good biocompatibility towards PC3 cells. Overall, since hydrogels based on CT-mediated two-component assemblies are very rare, our newly discovered NDI-Py hydrogels provide the chemical insights into the design of CT-induced hydrogelator and might facilitate various applications in biomedical engineering.
Fifth part we describe the blends of oppositely charged Py-gelators (Py-Glu and Py-Lys) resultant in formation of fluorescent physiological hydrogels with nanofibers architecture as evident from various microscopic and spectroscopic techniques. The formation of hydrogels display unique helical fibers morphology which clearly shows the significance of additional electrostatic interactions in self-assembly. Overall, this work illustrates the importance of two-component supramolecular co-assembled fluorescent hydrogels and their structure–morphology relationship, improved mechanical properties and biocompatibility and thus provides a new insight into the design of self-assembled nanomaterials.
In sixth part of the study, a new system of a NSAID drug (ketorolac) conjugate with peptides were studied. In general NSAID-capped supramolecular hydrogels are clinically useful as topical agents for treating inflammation and relieving pain and may have potential applications in sustained drug delivery. The Ketorolac based tripeptides illustrates a new approach to improve the COX-2/COX-1 selectivity ratio of Ket drug through controlling the stereochemistry of the chemical structures, which may have a wide range of future clinical applications in treating chronic inflammation.A series of anti-inflammatory supramolecular hydrogelators made of ketorolac/tripeptide conjugates that form supramolecular hydrogels at physiological pH. Our findings indicate ketorolac-capped tripeptide Ket-Gly-D-Phe-D-Phe shows reversal of COX selectivity which is a potential candidate for topical and therapeutic applications.
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In chapter-7 the synthesis and self-assemblying of a series of 4-piperidine 1, 8-naphthalene diimide based dipeptides were described.Most interesting discovery is that the self-assembly was greatly influenced by both pH and concentration for all hydrogelators. The self-assembly of PPNI-capped dipeptides, which is proceeded via π–π interactions and hydrogen bonding under aqueous conditions into nano-tubular structures were explained based on various spectroscopic and microscopic techniques. In particular, PPNI-FS having one hydroxyl group, which is self-assemble into well-defined supramolecular physiological hydrogel with a nano-tubular morphology in various conditions and good biocompatible material. Overall, this study illustrates the importance of the relationship between amino acid side chains and gelation conditions. This provides new insights into designs of new functional hydrogels, and may also facilitate various applications in bioengineering. Overall conclusions are contained in the last chapter.
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