Design and synthesis of stimuli responsive polymer based nanoparticles

Design and Synthesis of Stimuli-Responsive Polymer Based Nanoparticles Li Min (B. Eng. and M. Eng., Tianjin University) A Thesis Submitted for the Degree of Doctor of Philosophy Department of Chemical and Biomolecular Engineering National University of Singapore 2011 i Acknowledgement I feel it the greatest honor to express my sincerest thanks to my supervisors, Prof. Kang En-Tang and Associate Prof. Li Jun, for their inspired guidance, great patience, invaluable suggestions and constant supervision throughout my research studies. Their dedication, sincerity and enthusiasm to scientific research, and the invaluable knowledge I learned from them have greatly impressed me and will benefit me in my future career. I am also grateful to Prof. Neoh Koon-Gee for her kind advice and guidance in my research on cell culture work, and permission to access the cell cultivating equipments in her research lab. I am also thankful to my all colleagues and laboratory officers for their support and assistance. In particular, thanks to Mr. Li Guoliang, Mr. Xu Liqun, Dr. Wang Liang and Dr. Zhang Zhiguo for their kind help and assistance with some experimental work in my research studies. It is my pleasure to work with all of them. The research scholarship provided by National University of Singapore is also gratefully acknowledged. Finally, but not lest, I would like to give my special thanks to my wife, my son, my daughter, my parents, my brother and all my family members. Without their continuous love, support and encouragement, I would not continue my research study till now. ii Contents Acknowledgement ii Contents . iii Summary .vi Nomenclatures xi List of Schemes xiii List of Figures .xiv List of Tables xx Chapter Introduction .1 Chapter Literature Review 2.1 Stimuli-Responsive Polymers .6 2.1.1 Temperature-Responsive Polymers .7 2.1.2 pH-Responsive Polymers 2.1.3 Light-Responsive Polymers 10 2.1.4 Field-Responsive Polymers 11 2.1.5 Biologically-Responsive Polymers .12 2.2 Preparation Methods for Stimuli-Responsive Polymers .14 2.2.1 Atom Transfer Radical Polymerization (ATRP) .16 2.2.2 Reversible Addition–Fragmentation Chain Transfer (RAFT) Polymerization .19 2.2.3 Nitroxide-Mediated Radical Polymerization (NMRP) .24 2.3 Stimuli-Responsive Polymer Based Nanoparticles .26 2.3.1 Layer-by-Layer (LbL) Assembly 27 2.3.2 Self-Assembly of Amphiphilic Block Copolymers 29 2.3.3 Grafting of Polymers onto the Surface of Particles 32 iii 2.3.4 Emulsion Polymerization 34 Chapter Self-Assembly of Stimuli-Responsive and Fluorescent Comb-like Amphiphilic Copolymers .37 3.1 Self-Assembly of Stimuli-Responsive and Fluorescent Comb-like Amphiphilic Copolymers in Aqueous Media .38 3.1.1 Introduction .38 3.1.2 Experimental Section 40 3.1.3 Results and Discussion .46 3.1.4 Conclusions .65 3.2 pH-, Temperature-Responsive and Fluorescent Hybrid Hollow Nanospheres from Self-Assembly and Gelation of Comb-like Amphiphilic Copolymers 66 3.2.1 Introduction .66 3.2.2 Experimental Section 67 3.2.3 Results and Discussion .70 3.2.4 Conclusions .85 Chapter Mesoporous Silica Nanospheres with pH- and Temperature-Responsive Fluorescent Copolymer Brushes 86 4.1 Introduction .87 4.2 Experimental Section 88 4.3 Results and Discussion .93 4.4 Conclusions .113 Chapter Clickable Poly(Ester Amine) Dendrimer-Grafted Fe3O4 Nanoparticles Prepared via Successive Michael Addition and Alkyne-Azide Click Chemistry 114 5.1 Introduction .115 5.2 Experimental Section 117 iv 5.3 Results and Discussion .124 5.4 Conclusions .140 Chapter Mannose-Encapsulated and Poly(Thiolester Amine) Dendrimer-Grafted Fe3O4 Magnetic Nanoparticles Prepared via Successive Michael Addition and Thiol-Yne Click Chemistry 142 6.1 Introduction .143 6.2 Experimental Section 143 6.3 Results and Discussion .147 6.4 Conclusions .165 Chapter Conclusions and Recommendations for Futer Work .166 7.1 Conclusions .167 7.2 Recommendations for Future Research 170 References 172 List of Publications 213 v Summary In this work, stimuli-responsive polymer based nanoparticles were synthesized via three versatile techniques for fabrication of core-shell nanoparticles: self-assembly of amphphilic copolymers, “graft-to” method and “graft-from” method. For the self-assembly of amphiphilic copolymers, well-defined “comb-like” graft copolymers, P(NVK-co-VBC)-comb-P(DMAEMA-co-AAc), were first synthesized (P(NVK)= poly(N-vinylcarbazole); P(VBC)= poly(4-vinylbenzyl chloride); P(DMAEMA)= poly((2-dimethylamino)ethyl methacrylate); P(AAc)= poly(acrylic acid)). The P(NVK-co-VBC) copolymer backbone was prepared via free radical polymerization of NVK and VBC monomers. The side chains comprising of random copolymers of DMAEMA and tert-butyl acrylate (tBA) with controlled length and molecular composition were synthesized by “grafting from” the P(NVK-co-VBC) backbone, using the VBC units as the ATRP macroinitiators. The P(DMAEMA-co-AAc) copolymer side chains were subsequently obtained by the hydrolysis of the tert-butyl groups of P(NVK-co-VBC)-comb-P(DMAEMA-co-AAc) tBA units. comb-like The graft pH-sensitive copolymers is water-soluble and can be self-assembled in aqueous media into hollow vesicles with multi-walls, arising from the acid-base interaction of the AAc and DMAEMA units in the side chains. In addition to the unique molecular architecture, the copolymer vesicles exhibit reversible pH-dependence in size and fluorescence intensity in aqueous media. The vesicular morphology of the copolymer can be tuned by pH of the medium, the length of the hydrophilic P(DMAEMA-co-AAc) side chains, and the concentration of the copolymer solution. In comparison, P(NVK-co-VBC)-comb-P(NIPAAm-co-DMAEMA) comb-like graft copolymers were vi prepared (P(NIPAAm)= poly(N-isopropylacrylamide)). The P(NVK-co-VBC)-comb-P(NIPAAm-co-DMAEMA) graft copolymers have the same P(NVK-co-VBC) copolymer backbone P(NVK-co-VBC)-comb-P(DMAEMA-co-AAc) as the copolymers. The P(NIPAAm-co-DMAEMA) copolymer side chains of controlled length were synthesized via the ATRP of NIPAAm and DMAEMA monomers, using the VBC units of the backbone as the ATRP initiators. The pH- and temperature-responsive hollow spherical nanoparticles self-assembled from the comb-like graft copolymer P(NVK-co-VBC)-comb-P(NIPAAm-co-DMAEMA) are single-shelled due to the absence of acid-base side chain interaction. Furthermore, P(NVK-co-VBC)-comb-P(DMAEMA-co-MPS) comb-like graft copolymers were synthesized (P(MPS)= poly(3-(trimethoxysilyl)propyl methacrylate)). The P(NVK-co-VBC)-comb-P(DMAEMA-co-MPS) graft copolymers contain the same P(NVK-co-VBC) copolymer P(NVK-co-VBC)-comb-P(DMAEMA-co-AAc) backbone as copolymers. the The P(DMAEMA-co-MPS) copolymer side chains of controlled length were synthesized via the ATRP of DMAEMA and MPS monomers by “grafting from” the P(NVK-co-VBC) backbone, using the VBC units as the ATRP macroinitiators. The self-assembled hollow spherical nanoparticles from the pH- and temperature-responsive P(NVK-co-VBC)-comb-P(DMAEMA-co-MPS) copolymers were obtained in a tetrahydrofuran (THF)/water binary solvent. Gelation of the MPS units forms a polysilsesquioxane network in the shell of hollow nanospheres, giving rise to the shape-stable organic-inorganic hybrid hollow nanostructures. The size of the hybrid hollow nanoparticles can be tuned by pH and temperature of the dispersion vii medium and the length of the hydrophilic P(DMAEMA-co-MPS) side chains of the copolymers. In addition to the well-defined molecular architecture and morphology, the hybrid nanospheres also exhibit reversible pH- and temperature-dependence in fluorescence intensity in aqueous media. For the “graft-to” approach, temperature- and pH-responsive fluorescent copolymers P(DMAEMA-co-4VP) (P(4VP)= poly(4-vinylpyridine)) were first synthesized via ATRP, using a pyrene-containing fluorescent ATRP initiator. In aqueous media, P(DMAEMA-co-4VP) copolymers exhibit controllable switching in fluorescence intensity within the pH window of to 9, as well as in a heating–cooling cycle between 20 oC and 40 oC, suggesting their potential application as optical sensing materials. The copolymers were then treated by NaN3 to produce azide-functionalized groups. The azide-functionalized P(DMAEMA-co-4VP) copolymers were subsequently grafted to the surface of alkyne-functionalized mesoporous silica nanospheres (MSNs) via alkyne-azide “click chemistry” in the presence of copper (I) catalyst, giving rise to well-defined pH- and temperature-responsive fluorescent MSNs. The resultant stimuli-responsive fluorescent MSNs can be used for potential applications as controlled storage and release system. Click chemistry was then extended to the surface functionalization of Fe3O4 magnetic nanoparticles (MNPs) to prepare the magnetic metal/organic hybrid nanoparticles. MNPs, consisting of a Fe3O4 nanocore, a silica inner shell and dendritic poly(ester amine) (PEA) outer shell, were synthesized by the “graft-from” method. The silica inner shell was prepared via the inorganic sol-gel reaction of 3-aminopropyltriethoxysilane (APS). The dendritic PEA (the third generation, G3) viii outer shell was subsequently grafted via successive Michael addition reaction and alkyne-azide click chemistry of propargyl acrylate and 11-azido-3,6,9-trioxaundecan-1-amine (ATXDA), respectively. The grafted PEA dendrimer chains have “tree-like” branching structure with ester amine repeat units and alkyne-terminated groups. The so-obtained Fe3O4-silica-PEA hybrid nanoparticles exhibited good solubility in an aqueous medium and were superparamagnetic with a saturation magnetization (Ms) of 8.1 emu g-1. The Fe3O4-silica-PEA MNPs were pH-sensitive, leading to a pH-dependent hydrodynamic size in an aqueous medium. The Fe3O4-silica-PEA MNPs did not exhibit significant cytotoxicity towards 3T3 fibroblasts and RAW macrophage cells after 24 h of incubation. The uptake of Fe3O4-silica-PEA MNPs by macrophage cells was low, even in cultures with a relatively high concentration of the MNPs (e.g. 1.0 mg mL-1), suggesting good biocompatibility of the MNPs and their potential biomaterial applications. In addition, the preservation of alkyne-terminated groups in the grafted PEA dendrimers allows further functionalization of the MNPs via alkyne-azide click reaction for multipurpose applications. “Metal-free” thiol-yne click chemistry was also utilized to synthesize magnetic metal/organic hybrid nanoparticles. The 3-aminopropyltriethoxysilane (APS) was first coupled to the surface of Fe3O4 nanocores via a sol-gel reaction, giving rise to the amine-terminated magnetic nanocores. A dendritic poly(thiolester amine) (PTEA) shell was then grafted to the amine-terminated magnetic nanocores via alternating Michael addition and thiol-yne click chemistry of propargyl acrylate and cysteamine, respectively. The grafted PTEA dendrimer chains have “tree-like” branching structure with thiolester amine repeat units and alkyne-terminated groups. Mannose was ix subsequently clicked onto the PTEA dendrimer (the fourth generation, G4)-grafted MNPs via the thiol-yne click reaction between the thiolated mannose (2-mercaptoethyl α-D-mannopyranoside) and the perserved alkyne groups of the G4 dendrimer. The so-obtained Fe3O4-g-G4-mannose MNPs possessed a good solubility in an aqueous medium and were superparamagnetic with a Ms of 30.9 emu g-1. The Fe3O4-g-G4-mannose MNPs were pH-sensitive, leading to a controlled hydrodynamic size in the aqueous medium of pH 3-9. The Fe3O4-g-G4-mannose MNPs, as well as the PTEA dendrimer-functionalized MNPs, did not exhibit significant cytotoxicity towards 3T3 fibroblasts and RAW macrophage cells after 24 h of incubation, suggesting their good biocompatibility. In addition, the Fe3O4-g-G4-mannose MNPs show specific binding ability to concanavalin A (ConA), indicating their potential biomaterial applications as lectin separation or recognition agents. The “metal-free” synthesis method of successive Michael addition reaction and thiol-yne click chemistry can be applied for the functionalization of different substrates with PTEA dendrimers and allow the preparation of highly functionalized dendrimers under mild conditions. x brushes and self-assembled monolayers: Versatile platforms to control cell adhesion to biomaterials (Review), Biointerphases, 4, pp. 2427-2448. 2009 Relogio, P.; Charreyre, M. T.; Farinha, J. P. S.; Martinho, J. M. G.; Pichot, C. Well-defined polymer precursors synthesized by RAFT polymerization of N,N-dimethylacrylamide/N-acryloxysuccinimide: random and block copolymers, Polymer, 45, pp. 8639-8649. 2004 Reum, N.; Fink-Straube, C.; Klein, T.; Hartmann, R. W.; Lehr, C. M.; Schneider, M. Multilayer coating of gold nanoparticles with drug-polymer coadsorbates, Langmuir, 26, pp. 16901-16908. 2010 Robbes, A. S.; Jestin, J.; Meneau, F.; Dalmas, F.; Sandre, O.; Perez, J.; Boue, F.; Cousin, F. Homogeneous dispersion of magnetic nanoparticles aggregates in a PS nanocomposite: Highly reproducible hierarchical structure tuned by the nanoparticles' size, Macromolecules, 43, pp. 5785-5796. 2010 Rodriguez-Hernandez, J.; Checot, F.; Gnanou, Y.; Lecommandoux, S. Toward 'smart' nano-objects by self-assembly of block copolymers in solution, Prog. Polym. Sci., 30, pp. 691-724. 2005 Rowe, M. D.; Chang, C. C.; Thamm, D. H.; Kraft, S. L.; Harmon, J. F.; Vogt, A. P.; Sumerlin, B. S.; Boyes, S. G. Tuning the magnetic resonance imaging properties of positive contrast agent nanoparticles by surface modification with RAFT polymers, Langmuir, 25, pp. 9487-9499. 2009 Rowe, M. D.; Thamm, D. H.; Kraft, S. L.; Boyes, S. G. Polymer-modified gadolinium metal-organic framework nanoparticles used as multifunctional nanomedicines for the targeted imaging and treatment of cancer, Biomacromolecules, 10, pp. 983-993. 2009 Rueda, J.; Zschoche, S.; Komber, H.; Schmaljohann, D.; Voit, B. Synthesis and characterization of thermoresponsive graft copolymers of NIPAAm and 198 2-alkyl-2-oxazolines by the "grafting from" method, Macromolecules, 38, pp. 7330-7336. 2005 Rzaev, Z. M. O.; Dincer, S.; Piskin, E. Functional copolymers of N-isopropylacrylamide for bioengineering applications, Prog. Polym. Sci., 32, pp. 534-595. 2007 Sahoo, N. G.; Rana, S.; Cho, J. W.; Li, L.; Chan, S. H. Polymer nanocomposites based on functionalized carbon nanotubes, Prog. Polym. Sci., 35, pp. 837-867. 2010 Sanda, F.; Nakai, T.; Kobayashi, N.; Masuda, T. Synthesis of polyacetylenes having pendant carbazole groups and their photo- and electroluminescence properties, Macromolecules, 37, pp. 2703-2708. 2004 Sanjuan, S.; Tran, Y. Synthesis of random polyampholyte brushes by atom transfer radical polymerization, J. Polym. Sci., Part A: Polym. Chem., 46, pp. 4305-4319. 2008 Sanson, N.; Rieger, J. Synthesis of nanogels/microgels by conventional and controlled radical crosslinking copolymerization, Polym. Chem., 1, pp. 965-977. 2010 Santos, C. M.; Kumar, A.; Zhang, W.; Cai, C. Z. Functionalization of fluorous thin films via "click'' chemistry, Chem. Commun., pp. 2854-2856. 2009 Sauer, M.; Meier, W. Responsive nanocapsules, Chem. Commun., pp. 55-56. 2001 Sauer, M.; Streich, D.; Meier, W. pH-sensitive nanocontainers, Adv. Mater., 13, pp. 1649-1651. 2001 Savariar, E. N.; Thayumanavan, S. Controlled polymerization of N-isopropylacrylamide with an activated methacrylic ester, J. Polym. Sci., Part A: Polym. Chem., 42, pp. 6340-6345. 2004 Save, M.; Weaver, J. V. M.; Armes, S. P.; McKenna, P. Atom transfer radical polymerization of hydroxy-functional methacrylates at ambient temperature: Comparison of glycerol monomethacrylate with 2-hydroxypropyl methacrylate, 199 Macromolecules, 35, pp. 1152-1159. 2002 Sbai, M.; Lyazidi, S. A.; Lerner, D. A.; Delcastillo, B.; Martin, M. A. Modified β-cylclodextrins as enhancers of fluorescence emission of carbazole alkaloid derivatives, Analytica Chimica Acta, 303, pp. 47-55. 1995 Scherzinger, C.; Lindner, P.; Keerl, M.; Richtering, W. Cononsolvency of poly(N,N-diethylacrylamide) (PDEAAM) and poly(N-isopropylacrylamide) (PNIPAM) based microgels in water/methanol mixtures: copolymer vs core-shell microgel, Macromolecules, 43, pp. 6829-6833. 2010 Schierholz, K.; Givehchi, M.; Fabre, P.; Nallet, F.; Papon, E.; Guerret, O.; Gnanou, Y. Acrylamide-based amphiphilic block copolymers via nitroxide-mediated radical polymerization, Macromolecules, 36, pp. 5995-5999. 2003 Schilli, C.; Lanzendorfer, M. G.; Muller, A. H. E. Benzyl and cumyl dithiocarbamates as chain transfer agent in the RAFT polymerization of N-isopropylacrylamide. In situ FT-NIR and MALDI-TOF MS investigation, Macromolecules, 35, pp. 6819-6827. 2002 Schilli, C. M.; Zhang, M. F.; Rizzardo, E.; Thang, S. H.; Chong, Y. K.; Edwards, K.; Karlsson, G.; Muller, A. H. E. A new double-responsive block copolymer synthesized via RAFT polymerization: Poly(N-isopropylacrylamide)-block-poly(acrylic acid), Macromolecules, 37, pp. 7861-7866. 2004 Schmitt, F. J.; Park, C.; Simon, J.; Ringsdorf, H.; Israelachvili, J. Direct surface force and contact angle measurements of an adsorbed polymer with a lower critical solution temperature, Langmuir, 14, pp. 2838-2845. 1998 Schofield, C. L.; Haines, A. H.; Field, R. A.; Russell, D. A. Silver and gold glyconanoparticles for colorimetric bioassays, Langmuir, 22, pp. 6707-6711. 2006 Schuler, C.; Caruso, F. Decomposable hollow biopolymer-based capsules, 200 Biomacromolecules, 2, pp. 921-926. 2001 Schulte, T.; Siegenthaler, K. O.; Luftmann, H.; Letzel, M.; Studer, A. Nitroxide-mediated polymerization of N-isopropylacrylamide: Electrospray ionization mass spectrometry, matrix-assisted laser desorption ionization mass spectrometry, and multiple-angle laser light scattering studies on nitroxide-terminated poly-N-isopropylacrylamides, Macromolecules, 38, pp. 6833-6840. 2005 Senear, D. F.; Teller, D. C. Thermodynamics of concanavalin-A dimer-tetramer self-association - sedimentation equilibrium studies, Biochemistry, 20, pp. 3076-3083. 1981 Serrano-Ruiz, D.; Rangou, S.; Avgeropoulos, A.; Zafeiropoulos, N. E.; Lopez-Cabarcos, E.; Rubio-Retama, J. Synthesis and chemical modification of magnetic nanoparticles covalently bound to polystyrene-SiCl2-poly(2-vinylpyridine), J. Polym. Sci., Part B: Polym. Phys., 48, pp. 1668-1675. 2010 Sfika, V.; Tsitsilianis, C.; Kiriy, A.; Gorodyska, G.; Stamm, M. pH responsive heteroarm starlike micelles from double hydrophilic ABC terpolymer with ampholitic A and C blocks, Macromolecules, 37, pp. 9551-9560. 2004 Shchukin, D. G.; Sukhorukov, G. B.; Mohwald, H. Smart inorganic/organic nanocomposite hollow microcapsules, Angew. Chem. Int. Ed., 42, pp. 4472-4475. 2003 Shen, H. W.; Eisenberg, A. Control of architecture in block-copolymer vesicles, Angew. Chem. Int. Ed., 39, pp. 3310-3312. 2000 Shinoda, H.; Matyjaszewski, K.; Okrasa, L.; Mierzwa, M.; Pakula, T. Structural control of poly(methyl methacrylate)-g-poly(dimethylsiloxane) copolymers using controlled radical polymerization: Effect of the molecular structure on morphology and mechanical properties, Macromolecules, 36, pp. 4772-4778. 2003 Shiyan, S. D.; Bovin, N. V. Carbohydrate composition and immunomodulatory activity 201 of different glycoforms of α1-acid glycoprotein, Glycoconjugate J., 14, pp. 631-638. 1997 Sideratou, Z.; Tsiourvas, D.; Paleos, C. M. Quaternized poly(propylene imine) dendrimers as novel pH-sensitive controlled-release systems, Langmuir, 16, pp. 1766-1769. 2000 Simmons, M. R.; Yamasaki, E. N.; Patrickios, C. S. Cationic homopolymer model networks and star polymers: synthesis by group transfer polymerization and characterization of the aqueous degree of swelling, Polymer, 41, pp. 8523-8529. 2000 Slowing, II; Vivero-Escoto, J. L.; Wu, C. W.; Lin, V. S. Y. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers, Adv. Drug Deliver. Rev., 60, pp. 1278-1288. 2008 Smith, A. E.; Xu, X. W.; Abell, T. U.; Kirkland, S. E.; Hensarling, R. M.; McCormick, C. L. Tuning nanostructure morphology and gold nanoparticle "locking" of multi-responsive amphiphilic diblock copolymers, Macromolecules, 42, pp. 2958-2964. 2009 Smith, A. E.; Xu, X. W.; Kirkland-York, S. E.; Savin, D. A.; McCormick, C. L. "Schizophrenic" self-assembly of block copolymers synthesized via aqueous RAFT polymerization: From micelles to vesicles, Macromolecules, 43, pp. 1210-1217. 2010 Srinivas, M.; Aarntzen, E.; Bulte, J. W. M.; Oyen, W. J.; Heerschap, A.; de Vries, I. J. M.; Figdor, C. G. Imaging of cellular therapies, Adv. Drug Deliver. Rev., 62, pp. 1080-1093. 2010 Stoenescu, R.; Meier, W. Vesicles with asymmetric membranes from amphiphilic ABC triblock copolymers, Chem. Commun., pp. 3016-3017. 2002 Sun, P. J.; Zhang, Y.; Shi, L. Q.; Gan, Z. H. Thermosensitive nanoparticles self-assembled from PCL-b-PEO-b-PNIPAAm triblock copolymers and their potential 202 for controlled drug release, Macromol. Biosci., 10, pp. 621-631. 2010 Suwa, K.; Yamamoto, K.; Akashi, M.; Takano, K.; Tanaka, N.; Kunugi, S. Effects of salt on the temperature and pressure responsive properties of poly(N-vinylisobutyramide) aqueous solutions, Colloid. Polym. Sci., 276, pp. 529-533. 1998 Tan, K. L.; Woon, L. L.; Wong, H. K.; Kang, E. T.; Neoh, K. G. Surface modification of plasma-pretreated poly(tetrafluoroethylene) films by graft-copolymerization, Macromolecules, 26, pp. 2832-2836. 1993 Tanaka, Y.; Gong, J. P.; Osada, Y. Novel hydrogels with excellent mechanical performance, Prog. Polym. Sci., 30, pp. 1-9. 2005 Tang, C.; Russell, P. J.; Martiniello-Wilks, R.; Rasko, J. E. J.; Khatri, A. Concise review: nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?, Stem Cells, 28, pp. 1686-1702. 2010 Tang, C. B.; Hur, S. M.; Stahl, B. C.; Sivanandan, K.; Dimitriou, M.; Pressly, E.; Fredrickson, G. H.; Kramer, E. J.; Hawker, C. J. Thin film morphology of block copolymer blends with tunable supramolecular interactions for lithographic applications, Macromolecules, 43, pp. 2880-2889. 2010 Tao, W.; Yan, L. F. Thermogelling of highly branched poly(N-isopropylacrylamide), J. Appl. Polym. Sci., 118, pp. 3391-3399. 2010 Tartaj, P.; Serna, C. J. Synthesis of monodisperse superparamagnetic Fe/silica nanospherical composites, J. Am. Chem. Soc., 125, pp. 15754-15755. 2003 Tian, Y. C.; Fendler, J. H. Langmuir-Blodgett film formation from fluorescence-activated, surfactant-capped, size-selected CdS nanoparticles spread on water surfaces, Chem. Mater., 8, pp. 969-974. 1996 Tian, Y. Q.; Chen, C. Y.; Yip, H. L.; Wu, W. C.; Chen, W. C.; Jen, A. K. Y. Synthesis, 203 nanostructure, functionality, and application of polyfluorene-block-poly(N-isopropylacrylamide)s, Macromolecules, 43, pp. 282-291. 2010 Tjipto, E.; Quinn, J. F.; Caruso, F. Layer-by-layer assembly of weak-strong copolymer polyelectrolytes: A route to morphological control of thin films, J. Polym. Sci., Part A: Polym. Chem., 45, pp. 4341-4351. 2007 Traitel, T.; Cohen, Y.; Kost, J. Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions, Biomaterials, 21, pp. 1679-1687. 2000 Tsarevsky, N. V.; Bencherif, S. A.; Matyjaszewski, K. Graft copolymers by a combination of ATRP and two different consecutive click reactions, Macromolecules, 40, pp. 4439-4445. 2007 Tsavalas, J. G.; Schork, F. J.; de Brouwer, H.; Monteiro, M. J. Living radical polymerization by reversible addition-fragmentation chain transfer in ionically stabilized miniemulsions, Macromolecules, 34, pp. 3938-3946. 2001 Tsuji, S.; Kawaguchi, H. Temperature-sensitive hairy particles prepared by living radical graft polymerization, Langmuir, 20, pp. 2449-2455. 2004 Urien, M.; Erothu, H.; Cloutet, E.; Hiorns, R. C.; Vignau, L.; Cramail, H. Poly(3-hexylthiophene) based block copolymers prepared by "click" chemistry, Macromolecules, 41, pp. 7033-7040. 2008 Vallet-Regi, M.; Rámila, A.; del Real, R. P.; Pérez-Pariente, J. A new property of MCM-41: Drug delivery system, Chem. Mater., 13, pp. 308-311. 2001 Vargo, M. L.; Gulka, C. P.; Gerig, J. K.; Manieri, C. M.; Dattelbaum, J. D.; Marks, C. B.; Lawrence, N. T.; Trawick, M. L.; Leopold, M. C. Distance dependence of electron transfer kinetics for azurin protein adsorbed to monolayer protected nanoparticle film assemblies, Langmuir, 26, pp. 560-569. 2010 204 Vermonden, T.; Jena, S. S.; Barriet, D.; Censi, R.; van der Gucht, J.; Hennink, W. E.; Siegel, R. A. Macromolecular diffusion in self-assembling biodegradable thermosensitive hydrogels, Macromolecules, 43, pp. 782-789. 2010 Vihola, H.; Marttila, A. K.; Pakkanen, J. S.; Andersson, M.; Laukkanen, A.; Kaukonen, A. M.; Tenhu, H.; Hirvonen, J. Cell-polymer interactions of fluorescent polystyrene latex particles coated with thermosensitive poly (N-isopropylacrylamide) and poly (N-vinylcaprolactam) or grafted with poly(ethylene oxide)-macromonomer, Int. J. Pharm., 343, pp. 238-246. 2007 Vivero-Escoto, J. L.; Slowing, II; Wu, C. W.; Lin, V. S. Y. Photoinduced intracellular controlled release drug delivery in human cells by gold-capped mesoporous silica nanosphere, J. Am. Chem. Soc., 131, pp. 3462-3463. 2009 Vogt, A. P.; Sumerlin, B. S. Tuning the temperature response of branched poly(N-isopropylacrylamide) prepared by RAFT polymerization, Macromolecules, 41, pp. 7368-7373. 2008 Walther, A.; Goldmann, A. S.; Yelamanchili, R. S.; Drechsler, M.; Schmalz, H.; Eisenberg, A.; Müller, A. H. E. Multiple morphologies, phase transitions, and cross-linking of crew-cut aggregates of polybutadiene-block-poly(2-vinylpyridine) diblock copolymers, Macromolecules, 41, pp. 3254-3260. 2008 Wandera, D.; Wickramasinghe, S. R.; Husson, S. M. Stimuli-responsive membranes, J. Membr. Sci., 357, pp. 6-35. 2010 Wang, D.; Liu, T.; Yin, J.; Liu, S. Y. Stimuli-responsive fluorescent poly(N-isopropylacrylamide) microgels labeled with phenylboronic acid moieties as multifunctional ratiometric probes for glucose and temperatures, Macromolecules, 44, pp. 2282-2290. 2011 Wang, L.; Neoh, K. G.; Kang, E. T.; Shuter, B.; Wang, S. C. Biodegradable 205 magnetic-fluorescent magnetite/poly(DL-lactic acid-co-alpha,beta-malic acid) composite nanoparticles for stem cell labeling, Biomaterials, 31, pp. 3502-3511. 2010 Wang, L.; Neoh, K. G.; Kang, E. T.; Shuter, B.; Wang, S. C. Superparamagnetic hyperbranched polyglycerol-grafted Fe3O4 nanoparticles as a novel magnetic resonance imaging contrast agent: An in vitro assessment, Adv. Funct. Mater., 19, pp. 2615-2622. 2009 Wang, M.; Thanou, M. Targeting nanoparticles to cancer, Pharmacol. Res., 62, pp. 90-99. 2010 Wang, Q. A. Theory and simulation of the self-assembly of rod-coil block copolymer melts: recent progress, Soft Matter, 7, pp. 3711-3716. 2011 Wang, Y.; Xu, H.; Zhang, X. Tuning the amphiphilicity of building blocks: controlled self-assembly and disassembly for functional supramolecular materials, Adv. Mater., 21, pp. 2849-2864. 2009 Weaver, J. V. M.; Williams, R. T.; Royles, B. J. L.; Findlay, P. H.; Cooper, A. I.; Rannard, S. P. pH-Responsive branched polymer nanoparticles, Soft Matter, 4, pp. 985-992. 2008 Wen, Y. Q.; McLaughlin, C. K.; Lo, P. K.; Yang, H.; Sleiman, H. F. Stable gold nanoparticle conjugation to internal DNA positions: facile generation of discrete gold nanoparticle-DNA assemblies, Bioconjugate Chem., 21, pp. 1413-1416. 2010 Wijagkanalan, W.; Kawakami, S.; Hashida, M. Designing dendrimers for drug delivery and imaging: pharmacokinetic considerations, Pharm. Res., 28, pp. 1500-1519. 2011 Wurm, F.; Kilbinger, A. F. M. Polymeric Janus particles, Angew. Chem. Int. Ed., 48, pp. 8412-8421. 2009 Xiong, Q. F.; Ni, P. H.; Zhang, F.; Yu, Z. Q. Synthesis and characterization of 2-(dimethylamino)ethyl methacrylate homopolymers via aqueous RAFT 206 polymerization and their application in miniemulsion polymerization, Polym. Bull., 53, pp. 1-8. 2004 Xu, C.; Wayland, B. B.; Fryd, M.; Winey, K. I.; Composto, R. J. pH-responsive nanostructures assembled from amphiphilic block copolymers, Macromolecules, 39, pp. 6063-6070. 2006 Xu, F. J.; Cai, Q. J.; Li, Y. L.; Kang, E. T.; Neoh, K. G. Covalent immobilization of glucose oxidase on well-defined poly(glycidyl methacrylate)-Si(111) hybrids from surface-initiated atom-transfer radical polymerization, Biomacromolecules, 6, pp. 1012-1020. 2005 Xu, F. J.; Kang, E. T.; Neoh, K. G. LTV-induced coupling of 4-vinylbenzyl chloride on hydrogen-terminated Si(100) surfaces for the preparation of well-defined polymer-Si hybrids via surface-initiated ATRP, Macromolecules, 38, pp. 1573-1580. 2005 Xu, F. J.; Kang, E. T.; Neoh, K. G. pH- and temperature-responsive hydrogels from crosslinked triblock copolymers prepared via consecutive atom transfer radical polymerizations, Biomaterials, 27, pp. 2787-2797. 2006 Xu, F. J.; Li, J.; Yuan, S. J.; Zhang, Z. X.; Kang, E. T.; Neoh, K. G. Thermo-responsive porous membranes of controllable porous morphology from triblock copolymers of polycaprolactone and Poly(N-isopropylacrylamide) prepared by atom transfer radical polymerization, Biomacromolecules, 9, pp. 331-339. 2008 Xu, F. J.; Li, Y. L.; Kang, E. T.; Neoh, K. G. Heparin-coupled poly(poly(ethylene glycol) monomethacrylate)-Si(111) hybrids and their blood compatible surfaces, Biomacromolecules, 6, pp. 1759-1768. 2005 Xu, F. J.; Neoh, K. G.; Kang, E. T. Bioactive surfaces and biomaterials via atom transfer radical polymerization, Prog. Polym. Sci., 34, pp. 719-761. 2009 Xu, F. J.; Yuan, Z. L.; Kang, E. T.; Neoh, K. G. Branched fluoropolymer-Si hybrids via 207 surface-initiated ATRP of pentafluorostyrene on hydrogen-terminated Si(100) surfaces, Langmuir, 20, pp. 8200-8208. 2004 Xu, K.; Zhou, S. X.; Wu, L. γ-methacryloxypropyltrimethoxysilane-functionalized M. zirconia Dispersion of nanoparticles in UV-curable formulations and properties of their cured coatings, Prog. Org. Coat., 67, pp. 302-310. 2010 Xu, R.; Sun, G. Y.; Li, Q. Y.; Wang, E. B.; Gu, J. M. A dual-responsive superparamagnetic Fe3O4/Silica/PAH/PSS material used for controlled release of chemotherapeutic agent, keggin polyoxotungstate, PM-19, Solid State Sci., 12, pp. 1720-1725. 2010 Xu, X. W.; Flores, J. D.; McCormick, C. L. Reversible imine shell cross-linked micelles from aqueous RAFT-synthesized thermoresponsive triblock copolymers as potential nanocarriers for "pH-triggered" drug release, Macromolecules, 44, pp. 1327-1334. 2011 Yager, K. G.; Barrett, C. J. Novel photo-switching using azobenzene functional materials, J. Photochem. Photobiol., A, 182, pp. 250-261. 2006 Yamamoto, S.; Pietrasik, J.; Matyjaszewski, K. Temperature- and pH-responsive dense copolymer brushes prepared by ATRP, Macromolecules, 41, pp. 7013-7020. 2008 Yamato, M.; Utsumi, M.; Kushida, A.; Konno, C.; Kikuchi, A.; Okano, T. Thermo-responsive culture dishes allow the intact harvest of multilayered keratinocyte sheets without dispase by reducing temperature, Tissue Eng., 7, pp. 473-480. 2001 Yang, C.; Cheng, Y. L. RAFT synthesis of poly(N-isopropylacrylamide) and poly(methacrylic acid) homopolymers and block copolymers: Kinetics and characterization, J. Appl. Polym. Sci., 102, pp. 1191-1201. 2006 Yang, M.; Wang, W.; Yuan, F.; Zhang, X. W.; Li, J. Y.; Liang, F. X.; He, B. L.; Minch, 208 B.; Wegner, G. Soft vesicles formed by diblock codendrimers of poly(benzyl ether) and poly(methallyl dichloride), J. Am. Chem. Soc., 127, pp. 15107-15111. 2005 Yang, S. M.; Kim, S. H.; Lim, J. M.; Yi, G. R. Synthesis and assembly of structured colloidal particles, J. Mater. Chem., 18, pp. 2177-2190. 2008 Yap, H. P.; Hao, X. J.; Tjipto, E.; Gudipati, C.; Quinn, J. F.; Davis, T. P.; Barner-Kowollik, C.; Stenzel, M. H.; Caruso, F. Synthesis, multilayer film assembly, and capsule formation of macromolecularly engineered acrylic acid and styrene sulfonate block copolymers, Langmuir, 24, pp. 8981-8990. 2008 Yeh, K. M.; Lee, C. C.; Chen, Y. Host copolymers containing pendant carbazole and oxadiazole groups: Synthesis, characterization and optoelectronic applications for efficient green phosphorescent OLEDs, J. Polym. Sci., Part A: Polym. Chem., 46, pp. 5180-5193. 2008 Yin, X.; Hoffman, A. S.; Stayton, P. S. Poly(N-isopropylacrylamide-co-propylacrylic acid) copolymers that respond sharply to temperature and pH, Biomacromolecules, 7, pp. 1381-1385. 2006 Yonzon, C. R.; Jeoungf, E.; Zou, S. L.; Schatz, G. C.; Mrksich, M.; Van Duyne, R. P. A comparative analysis of localized and propagating surface plasmon resonance sensors: The binding of concanavalin a to a monosaccharide functionalized self-assembled monolayer, J. Am. Chem. Soc., 126, pp. 12669-12676. 2004 Yoo, M. K.; Sung, Y. K.; Lee, Y. M.; Cho, C. S. Effect of polyelectrolyte on the lower critical solution temperature of poly(N-isopropyl acrylamide) in the poly(NIPAAm-co-acrylic acid) hydrogel, Polymer, 41, pp. 5713-5719. 2000 Yoshida, R. Design of functional polymer gels and their application to biomimetic materials, Curr. Org. Chem., 9, pp. 1617-1641. 2005 Yoshida, R.; Uesusuki, Y. Biomimetic gel exhibiting self-beating motion in ATP 209 solution, Biomacromolecules, 6, pp. 2923-2926. 2005 You, Y. Z.; Hong, C. Y.; Pan, C. Y.; Wang, P. H. Synthesis of a dendritic core-shell nanostructure with a temperature-sensitive shell, Adv. Mater., 16, pp. 1953-1957. 2004 Yu, H. J.; Wang, L.; Chen, T. Novel organic/inorganic hybrid self-assembly aggregates of ferrocene-poly(styrene)-b-poly[3-(trimethyoxysilyl)propyl methacrylate], Eur. Polym. J., 45, pp. 639-642. 2009 Yu, K.; Zhang, L. F.; Eisenberg, A. Novel morphologies of ''crew-cut'' aggregates of amphiphilic diblock copolymers in dilute solution, Langmuir, 12, pp. 5980-5984. 1996 Yuan, J. J.; Ma, R.; Gao, Q.; Wang, Y. F.; Cheng, S. Y.; Feng, L. X.; Fan, Z. Q.; Jiang, L. Synthesis and characterization of polystyrene/poly(4-vinylpyridine) triblock copolymers by reversible addition-fragmentation chain transfer polymerization and their self-assembled aggregates in water, J. Appl. Polym. Sci., 89, pp. 1017-1025. 2003 Yusa, S.; Shimada, Y.; Mitsukami, Y.; Yamamoto, T.; Morishima, Y. Heat-induced association and dissociation behavior of amphiphilic diblock copolymers synthesized via reversible addition-fragmentation chain transfer radical polymerization, Macromolecules, 37, pp. 7507-7513. 2004 Zentner, G. M.; Rathi, R.; Shih, C.; McRea, J. C.; Seo, M. H.; Oh, H.; Rhee, B. G.; Mestecky, J.; Moldoveanu, Z.; Morgan, M.; Weitman, S. Biodegradable block copolymers for delivery of proteins and water-insoluble drugs, J. Controlled Release, 72, pp. 203-215. 2001 Zha, L. S.; Zhang, Y.; Yang, W. L.; Fu, S. K. Monodisperse temperature-sensitive microcontainers, Adv. Mater., 14, pp. 1090-1092. 2002 Zhang, H.; Ni, P. H.; He, J. L.; Liu, C. C. Novel fluoroalkyl end-capped amphiphilic diblock copolymers with pH/temperature response and self-assembly behavior, Langmuir, 24, pp. 4647-4654. 2008 210 Zhang, L.; Xue, H.; Gao, C. L.; Carr, L.; Wang, J. N.; Chu, B. C.; Jiang, S. Y. Imaging and cell targeting characteristics of magnetic nanoparticles modified by a functionalizable zwitterionic polymer with adhesive 3,4-dihydroxyphenyl-L-alanine linkages, Biomaterials, 31, pp. 6582-6588. 2010 Zhang, L. F.; Cheng, Z. P.; Zhou, N. C.; Shi, S. P.; Su, X. R.; Zhu, X. L. Synthesis of miktoarm dumbbell-like amphiphilic triblock copolymer by combination of consecutive RAFT polymerizations and ATRP, Polym. Bull., 62, pp. 11-22. 2009 Zhang, L. F.; Yu, K.; Eisenberg, A. Ion-induced morphological changes in ''crew-cut'' aggregates of amphiphilic block copolymers, Science, 272, pp. 1777-1779. 1996 Zhang, P.; Liu, Q. F.; Qing, A. X.; Sh, I. B.; Lu, M. G. Synthesis and characterization of core-shell-type polymeric micelles from diblock copolymers via reversible addition-fragmentation chain transfer, J. Polym. Sci., Part A: Polym. Chem., 44, pp. 3312-3320. 2006 Zhang, T. Z.; Li, T.; Nies, E.; Berghmans, H.; Ge, L. Q. Isothermal crystallization study on aqueous solution of poly(vinyl methyl ether) by DSC method, Polymer, 50, pp. 1206-1213. 2009 Zhang, Z. G.; Yuan, J. B.; Tang, H. J.; Tang, H.; Wang, L. N.; Zhang, K. L. Nearly monochromatic red electroluminescence from a nonconjugated polymer containing carbazole segments and phenanthroline [Eu(β-diketonate)3] moieties, J. Polym. Sci., Part A: Polym. Chem., 47, pp. 210-221. 2009 Zhao, B.; Zhu, L. Mixed polymer brush-grafted particles: A new class of environmentally responsive nanostructured materials, Macromolecules, 42, pp. 9369-9383. 2009 Zhao, L. Z.; Ma, R. J.; Li, J. B.; Li, Y.; An, Y. L.; Shi, L. Q. J- and H-Aggregates of 5,10,15,20-Tetrakis-(4-sulfonatophenyl)-porphyrin and Interconversion in 211 PEG-b-P4VP Micelles, Biomacromolecules, 9, pp. 2601-2608. 2008 Zhao, W. R.; Chen, H. R.; Li, Y. S.; Li, L.; Lang, M. D.; Shi, J. L. Uniform rattle-type hollow magnetic mesoporous spheres as drug delivery carriers and their sustained-release property, Adv. Funct. Mater., 18, pp. 2780-2788. 2008 Zheng, J.; Stevenson, M. S.; Hikida, R. S.; Van Patten, P. G. Influence of pH on dendrimer-protected nanoparticles, J. Phys. Chem. B, 106, pp. 1252-1255. 2002 Zheng, Q.; Pan, C. Y. Preparation and characterization of dendrimer-star PNIPAAM using dithiobenzoate-terminated PPI dendrimer via RAFT polymerization, Eur. Polym. J., 42, pp. 807-814. 2006 Zheng, Z. J.; Pan, C. Y.; Wang, D.; Liu, Y. Michael addition polymerizations of trifunctional amines with divinyl sulfone, Macromol. Chem. Phys., 206, pp. 2182-2189. 2005 Zhu, Y. T.; Yu, H. Z.; Zhu, J. T.; Zhao, G. Y.; Jiang, W.; Yang, X. D. Morphological transition of dry vesicles into onion-like multilamellar micelles induced through heating at high temperature, Chem. Phys. Lett., 460, pp. 257-260. 2008 Zou, P.; Shi, G. Y.; Pan, C. Y. Large-compound vesicle-encapsulated multiwalled carbon nanotubes: A unique route to nanotube composites, J. Polym. Sci., Part A: Polym. Chem., 47, pp. 3669-3679. 2009 212 List of Publications 1. Li M., Li G. L., Zhang Z. G., Li J., Neoh K. G and Kang E. T. Self-assembly of pH-responsive and fluorescent comb-like amphiphilic copolymers in aqueous media, Polymer, 51, pp 3377-3386, 2010. 2. Li M., Xu L. Q., Wang L., Wu Y. P., Li J., Neoh K. G and Kang E. T. Clickable poly(ester amine) dendrimer-grafted Fe3O4 nanoparticles prepared via successive Michael addition and alkyne-azide click chemistry, Polym. Chem., 2, pp 1312-1321, 2011. 3. Li G. L., Liu G., Li M., Wan D., Neoh K. G and Kang E. T. Organo- and water-dispersible graphene oxide-polymer nanosheets for organic electronic memory and gold nanocomposites, J. Phys. Chem. C, 114, pp 12742-12748, 2010. 4. Li G. L., Li M., Neoh K. G and Kang E. T. Hairy Hollow nanospheres of pH-responsive poly(methacrylic acid) shell and temperature-responsive poly(N-isopropylacrylamide) brushes, the 241st ACS National Meeting, Anaheim, CA, USA, 2011. 213 [...]... et al., 2009, Neiman and Varghese, 2011, Yoshida, 2005) The most widely-used classes of stimuli- responsive polymers are temperature -responsive polymers and pH -responsive polymers Other types of stimuli- responsive polymers, such as light -responsive polymers, field -responsive polymers and biologically -responsive polymers, will be mentioned as well 6 2.1.1 Temperature -Responsive Polymers Temperature is... (1)) and successive Michael addition (step (2)) and alkyne-azide click chemistry (step (3)) xiii List of Figures Figure 3.1 FT-IR spectra of (a) the P(NVK-co-VBC) copolymer, and the (b) KVDT3 copolymer, (c) KVDA3 copolymer and (d) KVND copolymer of Table 3.1 Figure 3.2 1H NMR spectra of (a) the P(NVK-co-VBC) copolymer in CDCl3, and the (b) KVDT3 copolymer in CDCl3, (c) KVDA3 copolymer and (d) KVND copolymer... aqueous media: (a) pH 3 and 25 oC, (b) pH 7 and 25 oC and (c) pH 7 and 40 oC The concentration of the copolymer solution was 0.1 wt% Figure 3.5 Effect of pH of aqueous media on the average hydrodynamic diameter (Dh) of the vesicles self-assembled from the (a) KVDA1 copolymer and the nanoparticles self-assembled from the (b) KVND copolymer of Table 3.1 The concentration of each copolymer solution was 0.1... Preparation Methods for Stimuli- Responsive Polymers Radical polymerization has played an important role in the development of stimuli- responsive polymer synthesis because of its widespread applications in the preparation of polymer- based biomaterials Conventional radical polymerizations, which are often called free radical processes, are the more commonly-used methods because a great deal of monomers is available... the comb-like copolymers of (1) KVDA1, (2) KVDA2, (3) KVDA3 and (4) KVDA4 of Table 3.1 at (a) pH 7 and (b) pH 5 The concentration of each copolymer solution was 0.1 wt% Figure 3.8 TEM images of the self-assembled vesicles of the KVDA3 copolymer of Table 3.1 at room temperature (25 oC), pH 7 and concentrations of (a) 0.04 wt%, (b) 0.05 wt%, (c) 0.1 wt% and (d) 0.8 wt% Figure 3.9 Effect of pH on the normalized... stimuli- responsive polymers, the methodologies for synthesis of stimuli- responsive polymers and the techniques for preparation of smart polymer based nanoparticles In Chapter 3, well-defined comb-like graft copolymers, consisting of a fluorescent hydrophobic poly((N-vinylcarbazole)-co-(4-vinylbenzyl chloride)) (P(NVK-co-VBC)) copolymer backbone and pH -responsive hydrophilic poly(((2-dimethylamino)ethyl... stimuli- responsive polymers can function as the principal materials of construction or the functional surface-grafting layer of responsive nanoparticles In this thesis, self-assembly of amphiphilic copolymers, “graft-to” and “graft-from” methods were utilized to synthesize stimuli- responsive nanoparticles Well-defined amphiphilic comb-like graft copolymers were synthesized via atom transfer radical polymerization... (d) KVND copolymer of Table 3.1 in D2O Figure 3.3 TEM images of the self-assembled vesicles of the KVDA1 copolymer of Table 3.1 in aqueous environment at room temperature (25 oC) and different pH: (a) pH = 3, (b) pH = 7 and (c, d) pH = 9 The concentration of each copolymer solution was 0.1 wt% Figure 3.4 TEM images of the self-assembled hollow nanoparticles of the KVND copolymer of Table 3.1 in aqueous... surface of MNPs The surface properties, pH-sensitivity, cytotoxicity and lectin binding ability of the resultant MNPs were investigated 4 Chapter 2 Literature Review 5 2.1 Stimuli- Responsive Polymers Stimuli- responsive polymers, which can respond in a dramatic way to a very minor change in their environment, are also called “smart” polymers The “response” of a polymer can appear in various ways Stimuli- responsive. .. Effect of pH on the normalized absorption and fluorescence (excitation wavelength at 295 nm) spectra of a 0.1 wt% aqueous solution of the KVDA3 copolymer of Table 3.1 xiv Figure 3.10 XPS widescan spectra of the (a) P(NVK-co-VBC) copolymer and (b) KVDM3 copolymer of Table 3.2 Figure 3.11 1H NMR spectra of the KVDM3 copolymer of Table 3.2 in CDCl3 Figure 3.12 TEM images of the cross-linked hybrid hollow nanospheres . i Design and Synthesis of Stimuli- Responsive Polymer Based Nanoparticles Li Min (B. Eng. and M. Eng., Tianjin University) A Thesis Submitted for the Degree of Doctor of. iv 2.3.4 Emulsion Polymerization 34 Chapter 3 Self-Assembly of Stimuli- Responsive and Fluorescent Comb-like Amphiphilic Copolymers 37 3.1 Self-Assembly of Stimuli- Responsive and Fluorescent. images of the self-assembled hollow nanoparticles of the KVND copolymer of Table 3.1 in aqueous media: (a) pH 3 and 25 o C, (b) pH 7 and 25 o C and (c) pH 7 and 40 o C. The concentration of