溫敏性高分子(Thermo-responsive polymers)是一種被稱為智能的材料，因為能夠靠著溫度變化改變表面的親水基與疏水基進行相變化，進而改變形狀與粒徑，應用範圍廣泛，例如在藥物傳遞、基因傳遞、組織工程、生物分離方面都有顯著的成果。
本研究嘗試利用具有生物相容性且成本較低的麥芽糖、麥芽三糖、麥芽糊精作為修飾由在生理條件下具有上限臨界溶解溫度(Upper critical solution temperature， UCST)的溫敏性高分子水溶性藍藻蛋白。經過紅外線光譜確認接枝，再以TNBSA測定與凝膠滲透層析儀計算接枝比例。由於水溶性藍藻蛋白相轉移點接近冰點較不利於應用，藉由接枝糖類使相轉移溫度上升，結果顯示接枝麥芽糖與麥芽三糖使得水溶性藍藻蛋白溶解度提升，導致相轉移點消失無法應用，而接枝麥芽糊精成功的增加分子內氫鍵，使相轉移點提高。我們探討在生理條件下不同的酸鹼值與濃度的條件來增加應用的發展性。我們利用穿透式電子顯微鏡確認粒子在37oC形狀為球狀，並且發現大多粒子粒徑落在300奈米以下。
本實驗目標期待這一系列新穎的溫敏性高分子能成功地做為藥物釋放載體有其潛在應用性。

Thermo-responsive polymer is one kind of smart materials. The changes in temperature can alter the hydrophilic−hydrophobic surface conduct to induce the phase change, and thereby alter polymer shapes. The applications of thermo-responsive polymers have been proposed and demonstrated in different fields, such as temperature-triggered drug release, gene delivery, tissue engineering and bio-separation.
In this study we used maltose, maltotriose and maltodextrin to modify water soluble cyanophycin, which has an upper critical solution temperature (UCST) under the physiological condition. The grafting ratios of cyanophycin-oligosaccharide conjugates were determined by colorimetry and gel permeation chromatography (GPC). Fourier transform infrared spectroscopy (FT-IR) was used to analyze the functional groups of the conjugates. Grafting oligosaccharides was found to enhance the phase transition point. The results showed that the grafting of maltose and maltotriose enhanced the solubility of cyanophycin which led to the disappearance of the phase transition point. The grafting of maltodextrin increased intramolecular hydrogen bonds and caused the increase in the phase transition point. We used a transmission electron microscope to confirm the particle sizes at 37oC.
This study showed that cyanophycin-oligosaccharide has the potential to be applied as a drug delivery system.

1. Seuring, J. and S. Agarwal, First Example of a Universal and Cost-Effective Approach: Polymers with Tunable Upper Critical Solution Temperature in Water and Electrolyte Solution. Macromolecules, 2012. 45(9): p. 3910-3918.
2. miscibility gap. 2009.
3. Ward, M.A. and T.K. Georgiou, Thermoresponsive Polymers for Biomedical Applications. Polymers, 2011. 3(4): p. 1215-1242.
4. Klouda, L. and A.G. Mikos, Thermoresponsive hydrogels in biomedical applications. Eur J Pharm Biopharm, 2008. 68(1): p. 34-45.
5. Kim, B., D. Hong, and W.V. Chang, LCST and UCST double-phase transitions of poly(N-isopropylacrylamide-co-2-acrylamidoglycolic acid)/poly(dimethylaminoethyl methacrylate) complex. Colloid and Polymer Science, 2014. 293(3): p. 699-708.
6. Huggins, M.L., Solutions of Long Chain Compounds. The Journal of Chemical Physics, 1941. 9(5): p. 440.
7. Stryuk, S. and B.A. Wolf, Chain Connectivity and Conformational Variability of Polymers: Clues to an Adequate Thermodynamic Description of their Solutions, 3. Macromolecular Chemistry and Physics, 2003. 204(16): p. 1948-1955.
8. Seuring, J. and S. Agarwal, Polymers with upper critical solution temperature in aqueous solution. Macromol Rapid Commun, 2012. 33(22): p. 1898-920.
9. Quiroz, F.G. and A. Chilkoti, Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers. Nat Mater, 2015. 14(11): p. 1164-71.
10. Chen, L., et al., Effects of polyelectrolyte complexation on the UCST of zwitterionic polymer. Polymer, 2000. 41(1): p. 141-147.
11. Lutz, J.-F., Polymerization of oligo(ethylene glycol) (meth)acrylates: Toward new generations of smart biocompatible materials. Journal of Polymer Science Part A: Polymer Chemistry, 2008. 46(11): p. 3459-3470.
12. Southall, N.T., K.A. Dill, and A.D.J. Haymet, A View of the Hydrophobic Effect. The Journal of Physical Chemistry B, 2002. 106(3): p. 521-533.
13. Maji, T., et al., Dual-Stimuli-Responsivel-Serine-Based Zwitterionic UCST-Type Polymer with Tunable Thermosensitivity. Macromolecules, 2015. 48(14): p. 4957-4966.
14. Wu, C. and X. Wang, Globule-to-Coil Transition of a Single Homopolymer Chain in Solution. Physical Review Letters, 1998. 80(18): p. 4092-4094.
15. Biswas, Y., et al., Tunable doubly responsive UCST-type phosphonium poly(ionic liquid): a thermosensitive dispersant for carbon nanotubes. Polym. Chem., 2016. 7(4): p. 867-877.
16. Yan, M., B. Li, and X. Zhao, Determination of critical aggregation concentration and aggregation number of acid-soluble collagen from walleye pollock (Theragra chalcogramma) skin using the fluorescence probe pyrene. Food Chemistry, 2010. 122(4): p. 1333-1337.
17. Jain, N., et al., Critical aggregation concentration in mixed solutions of anionic polyelectrolytes and cationic surfactants. Langmuir, 2004. 20(20): p. 8496-503.
18. Trivedi, R. and U.B. Kompella, Nanomicellar formulations for sustained drug delivery: strategies and underlying principles. Nanomedicine (Lond), 2010. 5(3): p. 485-505.
19. Zhang, X., et al., Synthesis and characterization of thermo- and pH-responsive double-hydrophilic diblock copolypeptides. Biomacromolecules, 2007. 8(11): p. 3557-67.
20. Könst, P.M., Production of nitrogen containing chemicals from cyanophycin. 2011, s.n.]: [S.l.
21. Wingard, L.L., et al., Cyanophycin Production in a Phycoerythrin-Containing Marine Synechococcus Strain of Unusual Phylogenetic Affinity. Applied and Environmental Microbiology, 2002. 68(4): p. 1772-1777.
22. Ziegler, K., et al., Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi- L-arginyl-poly- L-aspartate (cyanophycin). European Journal of Biochemistry, 1998. 254(1): p. 154-159.
23. Mooibroek, H., et al., Assessment of technological options and economical feasibility for cyanophycin biopolymer and high-value amino acid production. Applied Microbiology and Biotechnology, 2007. 77(2): p. 257-267.
24. Frommeyer, M., K. Bergander, and A. Steinbüchel, Guanidination of Soluble Lysine-Rich Cyanophycin Yields a Homoarginine-Containing Polyamide. Applied and environmental microbiology, 2014. 80(8): p. 2381-2389.
25. Neumann, K., et al., Production of cyanophycin, a suitable source for the biodegradable polymer polyaspartate, in transgenic plants. Plant Biotechnol J, 2005. 3(2): p. 249-58.
26. Voss, I., et al., Identification of the Anabaena sp. strain PCC7120 cyanophycin synthetase as suitable enzyme for production of cyanophycin in gram-negative bacteria like Pseudomonas putida and Ralstonia eutropha. Biomacromolecules, 2004. 5(4): p. 1588-95.
27. Koop, A., et al., Identification and Localization of Cyanophycin in Bacteria Cells via Imaging of the Nitrogen Distribution Using Energy-Filtering Transmission Electron Microscopy. Biomacromolecules, 2007. 8(9): p. 2675-2683.
28. Aboulmagd, E., F.B. Oppermann-Sanio, and A. Steinbchel, Molecular characterization of the cyanophycin synthetase from Synechocystis sp. strain PCC6308. Archives of Microbiology, 2000. 174(5): p. 297-306.
29. Oppermann-Sanio, F.B. and A. Steinbüchel, Occurrence, functions and biosynthesis of polyamides in microorganisms and biotechnological production. Naturwissenschaften, 2002. 89(1): p. 11-22.
30. Verma, M.L., Microbial Biosynthesis Of Biopolymers And Applications In The Biopharmaceutical, Biomedical And Food Industries.
31. Quigley, G.J., A. Sarko, and R.H. Marchessault, Crystal and molecular structure of maltose monohydrate. Journal of the American Chemical Society, 1970. 92(20): p. 5834-5839.
32. Roth, K. and W. Russey, Our Daily Bread — Part 3. ChemViews, 2013.
33. David W. Ball, J.W.H.a.R.J.S., The Basics of General, Organic, and Biological Chemistry, v. 1.0. March 2011
34. Hii, S.L., et al., Pullulanase: role in starch hydrolysis and potential industrial applications. Enzyme Res, 2012. :p. 921362.
35. Shanmugam, S., Enzyme Technology. 2009: p. P140.
36. Fang, Y., R. Takahashi, and K. Nishinari, Protein/polysaccharide cogel formation based on gelatin and chemically modified schizophyllan. Biomacromolecules, 2005. 6(6): p. 3202-8.
37. Hilliard, J.J., M.R. Maurizi, and L.D. Simon, Isolation and Characterization of the Phage T4 PinA Protein, an Inhibitor of the ATP-dependent Lon Protease ofEscherichia coli. Journal of Biological Chemistry, 1998. 273(1): p. 518-523.
38. Cordes, E.H. and W.P. Jencks, On the Mechanism of Schiff Base Formation and Hydrolysis. Journal of the American Chemical Society, 1962. 84(5): p. 832-837.
39. Cayot, P. and G. Tainturier, The quantification of protein amino groups by the trinitrobenzenesulfonic acid method: a reexamination. Anal Biochem, 1997. 249(2): p. 184-200.
40. Rödel, W., G. Rendina: Experimental Methods in Modern Biochemistry. 333 Seiten, 46 Abb., 65 Tab. Verlag W. B. Saunders Company, Philadelphia, London, Toronto 1971. Preis: 3,65 £. Food / Nahrung, 1972. 16(7): p. 807-808.
41. Brown, G.M., et al., Dodecatungstophosphoric acid hexahydrate, (H5O2+)3(PW12O403−). The true structure of Keggin's `pentahydrate' from single-crystal X-ray and neutron diffraction data. Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry, 1977. 33(4): p. 1038-1046.
42. Jennings, K.R., Spectrometric identification of organic compounds (Fifth Edition) R. M. SILVERSTEIN, G. C. BASSLER AND T. C. MORRILL. Wiley, New York, 1991. No. of pages: 430. ISBN 0471 63404 2. Price: £50.25, $76.10. Organic Mass Spectrometry, 1991. 26(9): p. 813-813.
43. Balu, R., et al., An16-resilin: an advanced multi-stimuli-responsive resilin-mimetic protein polymer. Acta Biomater, 2014. 10(11): p. 4768-77.
44. Tsavas, P., et al., Phase Equilibrium Calculations in Aqueous and Nonaqueous Mixtures of Sugars and Sugar Derivatives with a Group-Contribution Model. Industrial & Engineering Chemistry Research, 2004. 43(26): p. 8391-8399.
45. Lu, Y., et al., Origin of hysteresis observed in association and dissociation of polymer chains in water. Phys Chem Chem Phys, 2010. 12(13): p. 3188-94.
46. De, J., Drug delivery and nanoparticles: Applications and hazards. International Journal of Nanomedicine, 2008: p. 133.