Synthesis and Characterization of Functional π-Conjugated-capped Materials in Hydrogels

• Main Authors: Satish Kumar Talloj, 楊家明
• Other Authors: Lin, Hsin-Chieh
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/xr6kc3

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 === 108 === In the last two and half decades, supramolecular chemistry is growing extremely fast in its field which rely on the concept of self-assembly at the molecular level. Because supramolecular self assembly induced by non covalent interations is the fundamental driving force for the formations of organic nanostrcutures. Supramolecular hydrogels contains 99% of water, and water is the main constituent of cells, tissues and organs in human body, therefore the self assembled nanostructures generated from water as the medium should be an ideal candidate for any biomedical applications. In this thesis, we synthesized and characterized the supramolecular self assembled peptide hydrogels based on aromatic and aggregation induced emission (AIE) active chromophores and subsequently investigated their nanostructures and photophysical properties. We also developed a photo responsive gel degradation of biocompatible triblock co-block cross linked polymer for manipulating the hydrogel features in situ. I started this thesis by giving definitions and introduction to supramolecular hydrogels and v its potential applications by taking representative examples from the most cited literature, followed by current work. In chapter 3, we have demonstrated the first example of glucosamine-capped supramolecular hydrogel (PFB-F-Glu) self-assembled with one dimensional nanotubular morphology at physiological pH by conjugating glucosamine moiety at C-terminus and various fluorine substituted aromatic group at N-terminus of phenylalanine residue. From a systematic study on chemical structures, we discovered the glucosamine-capped supramolecular hydrogel (PFB-F-Glu) with one dimensional nanotubular structures at physiological pH. The selfassembly of newly discovered PFB-F-Glu motif is attributed to synergistic effect of - stacking and extensive intermolecular hydrogen bonding network in aqueous. Notably, PFB-FGlu nanotubes proved non-toxic to human mesenchymal stem cells (hMSCs) and thus showed to enhance hMSCs proliferation while maintaining its pluripotency. Retaining pluripotency capabilities provides potentially unlimited source of differentiated cells for the treatment of future cell therapies. Furthermore, hMSCs cultured on PFB-F-Glu are able to secrete paracrine factors that down-regulate pro-fibrotic gene expression in LPS-treated human skin fibroblasts which demonstrates that PFB-F-Glu nanotubes might have the potential to be used for wound healing applications. Overall, the chapter 3 addresses the importance of chemical design to generate supramolecular biomaterial and could be ideal candidate biomaterial for stem cell therapy. In chapters 4 and 5, we have designed a novel tetraphenylethylene (AIE) based dipeptide hydrogels. Particularly chapter 4 deals with the investigation of supramolecular nanostructure based on tetraphenylethylene capped dipeptide by pH controlled self-assembly. Here we report a systematic study of AIE-active tetraphenylethylene (TPE)-capped dipeptides self-assembled into various supramolecular nanostructures by simply altering the hydroxyl groups in the side chain of the amino acids. The self assembled nanostructures of these newly designed TPEdipeptides was studied at various pH and in dilute solutions by means of transmission electron vi microscopy (TEM). Interestingly, the hydrogel of TPE-Phe-Tyr is found to be the first example of TPE-capped dipeptide that has the capacity to self assemble into supramolecular nanotubes at physiological pH. More significantly, we observed the formation of hollow nanotubular morphologies at the same pH conditions. At the same time, the dilute solutions of TPE-Phe- Tyr also exhibited the formation of cylindrical nanotubes which could be an interesting candidate as drug delivery vehicle. In contrast, the hydrogels of TPE-Tyr-Phe and TPE-Tyr- Tyr exhibited the formations of self assembled nanoribbons and twisted nanobelts. The Circular dichroic (CD) and FTIR spectra reveal the formations of well ordered and β-sheet arrangement of nanostrcutures. Overall, from the chapter 4 we have demonstrated that self-assembling peptide incorporating AIEgens may inspire new insights for fabricating novel nanostrcutures by simply changing the amino acid sequence pattern opens up many potential applications including bioimaging. While chapter 5 focuses mainly on the synthetic study for preparing TPE-RED and TPENIR based dipeptide hydrogels for biological imaging. We developed an economic and high yielding synthetic protocol for the synthesis of TPE-RED emissive material. By incorporating suitable electron donors (D) and acceptors (A) at the periphery of the TPE core, we can tune the absorption and emission of organic conjugated molecules. The TPE-RED-FY can undergo self assembly at physiclogical pH to form nanovesicles which leads to opaque hydrogel. This newly designed TPE-RED-FY nanovesicles were uniformly distributed in the cytoplasm of CT- 36 cells (Colon cancer) after 90 minutes of incubationat 50 M concnetrations which indicates that this material can serve as a potential candidate for Bio-imaging. Interestingly, pH triggered and enzyme triggered hydrogelation of TPE-RED dipeptide resulted in the formation of nanovesicles for cell encapsulation and release or in targeted drug delivery applications. Finally, in chapter 6, we successfully synthesized two compounds with biocompatible triblock co-polymer F127 (ester and amide linkage) conjugated with Photolabile moiety (F127- PL) at chain ends with ~80% of conjugation and characterized by 1HNMR and FTIR. The vii F127-PL was cross-linked with small molecule acrylamide monomer by redox initiated radical polymerization that undergo photodegradation by UV light irradiation for 15 min, which was monitored by oscillatory rheometry. These materials might be helpful for cell encapsulation and release studies in vivo according to literature. More interestingly, the cross-linked polymeric hydrogel was incubated with culture medium (Dulbecco’s Modified Eagle Medium low glucose (DMEM-LG(89%)), 10% FBS, 1% Penicillin – steptomycin (PS)) at room temepearure and the hydrogels are stable up to 21 days. Hence, such biocompatible F127-with photodegradable crosslinked hydrogels with acrylamide through redox initiated radical mechanism and tailoring the mechanical properties of the hydrogels by non invasive method may find widespread applications in many bioengineering fields, including controlled bioactive molecule delivery, cell encapsulation for controlled threedimensional culture, and tissue engineering.