Temperature-responsive polymers: Synthesis, properties, and biomedical applications

Interest in temperature-responsive polymers has steadily grown over the past several decades, and numerous studies have been dedicated to developing temperature sensitive polymers that can be constructed into new smart materials for biomedical applications. Phase behavior of a temperature-responsive polymer plays a pivotal role in determining its biological performance in certain conditions. In addition to the additives (such as salts and proteins) in aqueous solutions, molecular weight, molecular weight distribution, and structural or compositional factors can also significantly affect the transition temperatures of the polymers. This review comprehensively describes well-established and newly developed synthetic strategies for preparing temperature-responsive polymers. The structural and compositional parameters that affect the transition temperatures and self-assembly behavior are discussed. Finally, the biomedical applications of the temperature-responsive polymers in drug delivery, immunotherapy, tissue engineering, and diagnosis are summarized.

[1]  T. Aida,et al.  Thermoresponsive actuation enabled by permittivity switching in an electrostatically anisotropic hydrogel. , 2015, Nature materials.

[2]  Ali Khademhosseini,et al.  Advances in engineering hydrogels , 2017, Science.

[3]  G. Qiao,et al.  Fenton-RAFT Polymerization: An "On-Demand" Chain-Growth Method. , 2017, Chemistry.

[4]  Chaoliang He,et al.  Novel pH- and Temperature-Responsive Block Copolymers with Tunable pH-Responsive Range , 2008 .

[5]  Cyrille Boyer,et al.  Copper-Mediated Living Radical Polymerization (Atom Transfer Radical Polymerization and Copper(0) Mediated Polymerization): From Fundamentals to Bioapplications. , 2016, Chemical reviews.

[6]  R. Yoshida,et al.  Amoeba-like self-oscillating polymeric fluids with autonomous sol-gel transition , 2017, Nature Communications.

[7]  Jiaming Zhuang,et al.  Multi-stimuli responsive macromolecules and their assemblies. , 2013, Chemical Society reviews.

[8]  K. Matyjaszewski,et al.  Controlled aqueous atom transfer radical polymerization with electrochemical generation of the active catalyst. , 2011, Angewandte Chemie.

[9]  Y. Harada,et al.  Hydrophilic fluorescent nanogel thermometer for intracellular thermometry. , 2009, Journal of the American Chemical Society.

[10]  K. Matyjaszewski,et al.  PEO-b-PNIPAM copolymers via SARA ATRP and eATRP in aqueous media , 2015 .

[11]  C. Chai,et al.  Metalloenzymatic radical polymerization using alkyl halides as initiators , 2011 .

[12]  K. Matyjaszewski,et al.  ICAR ATRP with ppm Cu Catalyst in Water , 2012 .

[13]  B. Sumerlin,et al.  Expanding the Scope of RAFT Polymerization: Recent Advances and New Horizons , 2015 .

[14]  O. Farokhzad,et al.  Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. , 2016, Chemical reviews.

[15]  Jeremiah A. Johnson,et al.  Photo-controlled growth of telechelic polymers and end-linked polymer gels. , 2013, Angewandte Chemie.

[16]  T. Okano,et al.  Novel bifunctional polymer with reactivity and temperature sensitivity , 2000, Journal of biomaterials science. Polymer edition.

[17]  Jiangtao Xu,et al.  A robust and versatile photoinduced living polymerization of conjugated and unconjugated monomers and its oxygen tolerance. , 2014, Journal of the American Chemical Society.

[18]  Guoying Zhang,et al.  Photo‐ and thermo‐responsive multicompartment hydrogels for synergistic delivery of gemcitabine and doxorubicin , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[19]  K. Matyjaszewski,et al.  Aqueous RDRP in the Presence of Cu0: The Exceptional Activity of CuI Confirms the SARA ATRP Mechanism , 2014 .

[20]  D. Haddleton,et al.  Polymerization-induced thermal self-assembly (PITSA) , 2014, Chemical science.

[21]  Ashutosh Chilkoti,et al.  Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumors after a single injection , 2009, Nature materials.

[22]  K. Matyjaszewski,et al.  Electrochemically mediated atom transfer radical polymerization ( e ATRP) , 2017 .

[23]  B. Sumerlin,et al.  New directions in thermoresponsive polymers. , 2013, Chemical Society reviews.

[24]  M. Stevens,et al.  Highly Controlled Open Vessel RAFT Polymerizations by Enzyme Degassing , 2014 .

[25]  M. Maeda,et al.  A polymer micelle responding to the protein kinase a signal , 2001 .

[26]  D. D. Mueller,et al.  Slow hydrogen-deuterium exchange in a non-.alpha.-helical polyamide , 1967 .

[27]  D. Haddleton,et al.  Photo-induced copper-mediated polymerization of methyl acrylate in continuous flow reactors , 2014 .

[28]  R. Kasper,et al.  Biocatalytic ATRP: Controlled radical polymerizations mediated by enzymes , 2013 .

[29]  Hongmei Li,et al.  Thermoresponsive block copolymer-protein conjugates prepared by grafting-from via RAFT polymerization. , 2011, Macromolecular rapid communications.

[30]  Samarth Kulkarni,et al.  Photoresponsive polymer–enzyme switches , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  B. Sumerlin Proteins as Initiators of Controlled Radical Polymerization: Grafting-from via ATRP and RAFT. , 2012, ACS macro letters.

[32]  K. Matyjaszewski,et al.  Diminishing catalyst concentration in atom transfer radical polymerization with reducing agents , 2006, Proceedings of the National Academy of Sciences.

[33]  A. Chilkoti,et al.  A brush-polymer conjugate of exendin-4 reduces blood glucose for up to five days and eliminates poly(ethylene glycol) antigenicity , 2016, Nature Biomedical Engineering.

[34]  N. Bruns,et al.  Controlling Enzymatic Polymerization from Surfaces with Switchable Bioaffinity. , 2017, Biomacromolecules.

[35]  T. Niidome,et al.  A peptide sequence controls the physical properties of nanoparticles formed by peptide-polymer conjugates that respond to a protein kinase a signal. , 2005, Bioconjugate chemistry.

[36]  David J. Lunn,et al.  Engineering live cell surfaces with functional polymers via cytocompatible controlled radical polymerization , 2017, Nature Chemistry.

[37]  Christopher B. Howard,et al.  An EGFR targeting nanoparticle self assembled from a thermoresponsive polymer , 2015 .

[38]  Thomas Maschmeyer,et al.  Rapid and quantitative one-pot synthesis of sequence-controlled polymers by radical polymerization , 2013, Nature Communications.

[39]  K. Matyjaszewski,et al.  Simplified electrochemically mediated atom transfer radical polymerization using a sacrificial anode. , 2015, Angewandte Chemie.

[40]  R. Hayward,et al.  Dynamic display of biomolecular patterns through an elastic creasing instability of stimuli-responsive hydrogels. , 2010, Nature materials.

[41]  Krzysztof Matyjaszewski,et al.  ATRP in the design of functional materials for biomedical applications. , 2012, Progress in polymer science.

[42]  Hua Wei,et al.  Self-assembled, thermosensitive micelles of a star block copolymer based on PMMA and PNIPAAm for controlled drug delivery. , 2007, Biomaterials.

[43]  C. Chai,et al.  PolyPEGA with predetermined molecular weights from enzyme-mediated radical polymerization in water. , 2011, Chemical communications.

[44]  Wah Chiu,et al.  Interbilayer-Crosslinked Multilamellar Vesicles as Synthetic Vaccines for Potent Humoral and Cellular Immune Responses , 2011, Nature materials.

[45]  Y. Harada,et al.  Intracellular temperature mapping with a fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy , 2012, Nature Communications.

[46]  Taolei Sun,et al.  Biomimetic Smart Interface Materials for Biological Applications , 2011, Advanced materials.

[47]  Zhen Gu,et al.  Synthetic beta cells for fusion-mediated dynamic insulin secretion. , 2018, Nature chemical biology.

[48]  Yao-Xin Lin,et al.  General Approach of Stimuli-Induced Aggregation for Monitoring Tumor Therapy. , 2017, ACS nano.

[49]  P. Théato,et al.  Activated Ester Containing Polymers: Opportunities and Challenges for the Design of Functional Macromolecules. , 2016, Chemical reviews.

[50]  S. Emelianov,et al.  Dynamic contrast-enhanced photoacoustic imaging using photothermal stimuli-responsive composite nanomodulators , 2017, Nature Communications.

[51]  G. López,et al.  A low-cost, rapid deposition method for "smart" films: applications in mammalian cell release. , 2010, ACS applied materials & interfaces.

[52]  Krzysztof Matyjaszewski,et al.  Macromolecular engineering by atom transfer radical polymerization. , 2014, Journal of the American Chemical Society.

[53]  Hua Wei,et al.  Thermo-sensitive polymeric micelles based on poly(N-isopropylacrylamide) as drug carriers , 2009 .

[54]  Krzysztof Matyjaszewski,et al.  Temporal Control in Mechanically Controlled Atom Transfer Radical Polymerization Using Low ppm of Cu Catalyst. , 2017, ACS macro letters.

[55]  Farzad Seidi,et al.  Horseradish peroxidase as a catalyst for atom transfer radical polymerization. , 2011, Macromolecular rapid communications.

[56]  Y. Miyahara,et al.  Synthetic “smart gel” provides glucose-responsive insulin delivery in diabetic mice , 2017, Science Advances.

[57]  Florian D Jochum,et al.  Temperature- and light-responsive smart polymer materials. , 2013, Chemical Society reviews.

[58]  M. C. Stuart,et al.  Emerging applications of stimuli-responsive polymer materials. , 2010, Nature materials.

[59]  K. Matyjaszewski,et al.  Bioinspired iron-based catalyst for atom transfer radical polymerization. , 2013, Angewandte Chemie.

[60]  T. Okano,et al.  Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate). , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[61]  Maud Save,et al.  RAFT Copolymerization of Vinyl Acetate and N-Vinylcaprolactam: Kinetics, Control, Copolymer Composition, and Thermoresponsive Self-Assembly , 2016 .

[62]  Yi Wang,et al.  Facile Synthesis of Peptide Cross-Linked Nanogels for Tumor Metastasis Inhibition , 2018 .

[63]  A. Chilkoti,et al.  Effects of Hofmeister anions on the phase transition temperature of elastin-like polypeptides. , 2008, The journal of physical chemistry. B.

[64]  Zesheng An,et al.  Glucose oxidase deoxygenation−redox initiation for RAFT polymerization in air , 2017 .

[65]  E. Malmström,et al.  Thermo-responsive cellulose-based architectures: tailoring LCST using poly(ethylene glycol) methacrylates , 2011 .

[66]  Taolei Sun,et al.  Dynamic biointerfaces: from recognition to function. , 2015, Small.

[67]  B. Sumerlin,et al.  Temperature-regulated activity of responsive polymer-protein conjugates prepared by grafting-from via RAFT polymerization. , 2008, Journal of the American Chemical Society.

[68]  Farzad Seidi,et al.  ATRPases: using nature's catalysts in atom transfer radical polymerizations , 2012 .

[69]  Xueliang Li,et al.  Enzyme-Assisted Photoinitiated Polymerization-Induced Self-Assembly: An Oxygen-Tolerant Method for Preparing Block Copolymer Nano-Objects in Open Vessels and Multiwell Plates , 2017 .

[70]  Zhaowei Chen,et al.  Leveraging Engineering of Cells for Drug Delivery. , 2018, Accounts of chemical research.

[71]  Yao-Xin Lin,et al.  Nanoantagonists with nanophase-segregated surfaces for improved cancer immunotherapy. , 2018, Biomaterials.

[72]  M. Cunningham,et al.  ARGET ATRP of BMA and BA: Exploring Limitations at Low Copper Levels , 2012 .

[73]  K. Matyjaszewski,et al.  A Breathing Atom-Transfer Radical Polymerization: Fully Oxygen-Tolerant Polymerization Inspired by Aerobic Respiration of Cells. , 2018, Angewandte Chemie.

[74]  Molly M Stevens,et al.  Synthetic polymer scaffolds for tissue engineering. , 2009, Chemical Society reviews.

[75]  K. Matyjaszewski,et al.  ARGET ATRP Synthesis of Thermally Responsive Polymers with Oligo(ethylene oxide) Units , 2008 .

[76]  A. Chilkoti,et al.  One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer , 2017, Nature Biomedical Engineering.

[77]  You Han Bae,et al.  Thermogelling aqueous solutions of alternating multiblock copolymers of poly(L-lactic acid) and poly(ethylene glycol). , 2006, Biomacromolecules.

[78]  R. B. Grubbs,et al.  Shape-changing polymer assemblies. , 2013, Chemical Society reviews.

[79]  Ke Wang,et al.  A New Family of Thermo-, pH-, and CO2-Responsive Homopolymers of Poly[Oligo(ethylene glycol) (N-dialkylamino) methacrylate]s , 2017 .

[80]  C. Barner‐Kowollik,et al.  50th Anniversary Perspective: Polymer Functionalization , 2017 .

[81]  Hao Wang,et al.  Intracellular construction of topology-controlled polypeptide nanostructures with diverse biological functions , 2017, Nature Communications.

[82]  Linqi Shi,et al.  Maintenance of amyloid β peptide homeostasis by artificial chaperones based on mixed-shell polymeric micelles. , 2014, Angewandte Chemie.

[83]  Rajamani Lakshminarayanan,et al.  Biodegradable Thermogelling Polymers: Working Towards Clinical Applications , 2014, Advanced healthcare materials.

[84]  J. Vacanti,et al.  Tissue engineering. , 1993, Science.

[85]  C. van Nostrum,et al.  Triggered destabilisation of polymeric micelles and vesicles by changing polymers polarity: an attractive tool for drug delivery. , 2007, Journal of Controlled Release.

[86]  Krzysztof Matyjaszewski,et al.  Nanostructured functional materials prepared by atom transfer radical polymerization , 2009, Nature Chemistry.

[87]  C. McCormick,et al.  Direct Synthesis of Thermally Responsive DMA/NIPAM Diblock and DMA/NIPAM/DMA Triblock Copolymers via Aqueous, Room Temperature RAFT Polymerization† , 2006 .

[88]  M. Stevens,et al.  Combinatorial Low-Volume Synthesis of Well-Defined Polymers by Enzyme Degassing. , 2016, Angewandte Chemie.

[89]  B. Sumerlin,et al.  Grafting-From Proteins Using Metal-Free PET-RAFT Polymerizations under Mild Visible-Light Irradiation. , 2017, ACS macro letters.

[90]  Yao-Xin Lin,et al.  Thermo-Controlled in Situ Phase Transition of Polymer-Peptides on Cell Surfaces for High-Performance Proliferative Inhibition. , 2016, ACS applied materials & interfaces.

[91]  K. Renggli,et al.  Filling polymersomes with polymers by peroxidase-catalyzed atom transfer radical polymerization. , 2015, Macromolecular rapid communications.

[92]  C. Barner‐Kowollik,et al.  In situ formation of protein-polymer conjugates through reversible addition fragmentation chain transfer polymerization. , 2007, Angewandte Chemie.

[93]  Hong Chen,et al.  Combining surface topography with polymer chemistry: Exploring new interfacial biological phenomena , 2014 .

[94]  Françoise M. Winnik,et al.  Poly(N-isopropylacrylamide) Phase Diagrams: Fifty Years of Research , 2016 .

[95]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[96]  D. Weitz,et al.  Bioinspired graphene membrane with temperature tunable channels for water gating and molecular separation , 2017, Nature Communications.

[97]  C. Barner‐Kowollik,et al.  Well-defined protein-polymer conjugates via in situ RAFT polymerization. , 2007, Journal of the American Chemical Society.

[98]  Y. Kotsuchibashi,et al.  Dual-temperature and pH responsive (ethylene glycol)-based nanogels via structural design , 2014 .

[99]  Martin Kröger,et al.  Poly(N-isopropylacrylamide) Phase Diagrams: Fifty Years of Research. , 2015, Angewandte Chemie.

[100]  M. Sefton,et al.  Tissue engineering. , 1998, Journal of cutaneous medicine and surgery.

[101]  Michael Y. Gerner,et al.  In vivo characterization of the physicochemical properties of TLR agonist delivery that enhance vaccine immunogenicity , 2015, Nature Biotechnology.

[102]  K. Matyjaszewski,et al.  Thermally Responsive P(M(EO)2MA-co-OEOMA) Copolymers via AGET ATRP in Miniemulsion , 2010 .

[103]  Cameron Alexander,et al.  Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling , 2014, Nature materials.

[104]  K. Matyjaszewski,et al.  Photomediated controlled radical polymerization , 2016 .

[105]  Hongmei Li,et al.  Block copolymer conjugates prepared by sequentially grafting from proteins via RAFT , 2011 .

[106]  Younan Xia,et al.  Gold nanocages covered by smart polymers for controlled release with near-infrared light , 2009, Nature materials.

[107]  Sébastien Perrier,et al.  Smart hybrid materials by conjugation of responsive polymers to biomacromolecules. , 2015, Nature materials.

[108]  D. Varadharajan,et al.  Triple Hydrophilic UCST–LCST Block Copolymers , 2016 .

[109]  Li Zhang,et al.  Low-Temperature Synthesis of Thermoresponsive Diblock Copolymer Nano-Objects via Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA) using Thermoresponsive Macro-RAFT Agents. , 2016, Macromolecular rapid communications.

[110]  A. P. de Silva,et al.  Fluorescent molecular thermometers based on polymers showing temperature-induced phase transitions and labeled with polarity-responsive benzofurazans. , 2003, Analytical chemistry.

[111]  K. Matyjaszewski,et al.  Electrochemically Mediated Atom Transfer Radical Polymerization , 2011, Science.

[112]  Austin J. Graham,et al.  Shewanella oneidensis as a living electrode for controlled radical polymerization , 2018, Proceedings of the National Academy of Sciences.

[113]  Herbert H. Hooper,et al.  SWELLING EQUILIBRIA FOR WEAKLY IONIZABLE, TEMPERATURE-SENSITIVE HYDROGELS , 1991 .

[114]  Lin Yu,et al.  Injectable hydrogels as unique biomedical materials. , 2008, Chemical Society reviews.

[115]  A. Jonas,et al.  Temperature‐Responsive Polymer Brushes Switching from Bactericidal to Cell‐Repellent , 2010, Advanced materials.

[116]  R. Chapman,et al.  An Oxygen-Tolerant PET-RAFT Polymerization for Screening Structure-Activity Relationships. , 2018, Angewandte Chemie.

[117]  M. Ward,et al.  Thermoresponsive Polymers for Biomedical Applications , 2011 .