Stimuli-responsive copolymer solution and surface assemblies for biomedical applications.

Stimuli-responsive polymeric materials is one of the fastest growing fields of the 21st century, with the annual number of papers published more than quadrupling in the last ten years. The responsiveness of polymer solution assemblies and surfaces to biological stimuli (e.g. pH, reduction-oxidation, enzymes, glucose) and externally applied triggers (e.g. temperature, light, solvent quality) shows particular promise for various biomedical applications including drug delivery, tissue engineering, medical diagnostics, and bioseparations. Furthermore, the integration of copolymer architectures into stimuli-responsive materials design enables exquisite control over the locations of responsive sites within self-assembled nanostructures. The combination of new synthesis techniques and well-defined copolymer self-assembly has facilitated substantial developments in stimuli-responsive materials in recent years. In this tutorial review, we discuss several methods that have been employed to synthesize self-assembling and stimuli-responsive copolymers for biomedical applications, and we identify common themes in the response mechanisms among the targeted stimuli. Additionally, we highlight parallels between the chemistries used for generating solution assemblies and those employed for creating copolymer surfaces.

[1]  T. Reineke,et al.  Membrane and nuclear permeabilization by polymeric pDNA vehicles: efficient method for gene delivery or mechanism of cytotoxicity? , 2012, Molecular Pharmaceutics.

[2]  B. Narasimhan,et al.  High-throughput analysis of protein stability in polyanhydride nanoparticles. , 2010, Acta biomaterialia.

[3]  Emily A. Hoff,et al.  Stimuli-responsive peptide-based ABA-triblock copolymers: unique morphology transitions with pH. , 2012, Macromolecular rapid communications.

[4]  S. Minko Responsive Polymer Brushes , 2006 .

[5]  Kato L. Killops,et al.  Nanopatterning Biomolecules by Block Copolymer Self-Assembly. , 2012, ACS macro letters.

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

[7]  Zhiyuan Zhong,et al.  Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[8]  Erik Wischerhoff,et al.  Controlled cell adhesion on PEG-based switchable surfaces. , 2008, Angewandte Chemie.

[9]  K. Uhrich,et al.  Design and Synthesis of Fast-Degrading Poly(anhydride-esters). , 2009, Macromolecular rapid communications.

[10]  Xi Zhang,et al.  Side-chain selenium-containing amphiphilic block copolymers: redox-controlled self-assembly and disassembly† , 2012 .

[11]  Tao Chen,et al.  Stimulus-responsive polymer brushes on surfaces: Transduction mechanisms and applications , 2010 .

[12]  P. Stayton,et al.  Diblock copolymers with tunable pH transitions for gene delivery. , 2012, Biomaterials.

[13]  W. Nie,et al.  Facile synthesis and responsive behavior of PDMS-b-PEG diblock copolymer brushes via photoinitiated “thiol-ene” click reaction , 2012 .

[14]  Martin Müller,et al.  Oxidation-responsive polymeric vesicles , 2004, Nature materials.

[15]  C. Ober,et al.  Photo-switchable polyelectrolyte brush for dual protein patterning , 2011 .

[16]  T. Okano,et al.  Temperature-responsive cell culture surfaces enable "on-off" affinity control between cell integrins and RGDS ligands. , 2004, Biomacromolecules.

[17]  Harm-Anton Klok,et al.  Standing on the shoulders of Hermann Staudinger: Post‐polymerization modification from past to present , 2013 .

[18]  C. R. Becer,et al.  Thermo-Induced Self-Assembly of Responsive Poly(DMAEMA‑b‑DEGMA) Block Copolymers into Multi- and Unilamellar Vesicles , 2012 .

[19]  S Thayumanavan,et al.  Multi-stimuli sensitive amphiphilic block copolymer assemblies. , 2009, Journal of the American Chemical Society.

[20]  Lei Gao,et al.  Core extractable nano‐objects: Manipulating triblock copolymer micelles , 2012 .

[21]  S. Pun,et al.  Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[22]  Yolonda L Colson,et al.  Biologically Responsive Polymeric Nanoparticles for Drug Delivery , 2012, Advanced materials.

[23]  P. Hammond Building biomedical materials layer-by-layer , 2012 .

[24]  Kristi S Anseth,et al.  Advances in bioactive hydrogels to probe and direct cell fate. , 2012, Annual review of chemical and biomolecular engineering.

[25]  Kai Yu,et al.  Effect of block sequence and block length on the stimuli-responsive behavior of polyampholyte brushes: hydrogen bonding and electrostatic interaction as the driving force for surface rearrangement , 2009 .

[26]  H. Frey,et al.  From an epoxide monomer toolkit to functional PEG copolymers with adjustable LCST behavior. , 2011, Macromolecular rapid communications.

[27]  Jean-François Gohy,et al.  Light-responsive block copolymers. , 2010, Macromolecular rapid communications.

[28]  Jin-Zhi Du,et al.  Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. , 2011, Journal of the American Chemical Society.

[29]  Jinying Yuan,et al.  Schiff's base as a stimuli-responsive linker in polymer chemistry , 2012 .

[30]  B. Mattiasson,et al.  Interaction of sugars, polysaccharides and cells with boronate‐containing copolymers: from solution to polymer brushes , 2006, Journal of molecular recognition : JMR.

[31]  Thomas H. Epps,et al.  Structural changes in block copolymer micelles induced by cosolvent mixtures. , 2011, Soft matter.

[32]  Zhiyuan Zhong,et al.  pH-Sensitive degradable polymersomes for triggered release of anticancer drugs: a comparative study with micelles. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[33]  Mark Dewhirst,et al.  Doxorubicin-conjugated chimeric polypeptide nanoparticles that respond to mild hyperthermia. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Ryan C. Hayward,et al.  Tailored Assemblies of Block Copolymers in Solution: It Is All about the Process , 2010 .

[35]  E. W. Meijer,et al.  Functional Supramolecular Polymers , 2012, Science.

[36]  T. Reineke,et al.  Exploring the mechanism of plasmid DNA nuclear internalization with polymer-based vehicles. , 2012, Molecular pharmaceutics.

[37]  J. Gwyther,et al.  Electrochemically Triggered Selective Adsorption of Biotemplated Nanoparticles on Self‐Assembled Organometallic Diblock Copolymer Thin Films , 2012 .

[38]  Mary E Napier,et al.  More effective nanomedicines through particle design. , 2011, Small.

[39]  F. Bates,et al.  Polymersomes functionalized via “click” chemistry with the fibronectin mimetic peptides PR_b and GRGDSP for targeted delivery to cells with different levels of α5β1 expression , 2012 .

[40]  A. M. Rush,et al.  Programmable shape-shifting micelles. , 2010, Angewandte Chemie.

[41]  P. Messersmith,et al.  Catechol Polymers for pH-Responsive, Targeted Drug Delivery to Cancer Cells , 2011, Journal of the American Chemical Society.

[42]  P. Théato,et al.  pH-switchable polymer nanostructures for controlled release , 2012 .

[43]  J. Benoit,et al.  Magnetic nanoparticles coated by temperature responsive copolymers for hyperthermia , 2008 .

[44]  Donghui Zhang,et al.  Polypeptoid Materials: Current Status and Future Perspectives , 2012 .

[45]  A. Heise,et al.  Selective enzymatic degradation of self-assembled particles from amphiphilic block copolymers obtained by the combination of N-carboxyanhydride and nitroxide-mediated polymerization. , 2011, Biomacromolecules.

[46]  L. Korley,et al.  Bioinspired Polymeric Nanocomposites , 2010 .

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

[48]  Yue Zhao,et al.  Block copolymer micelles with a dual-stimuli-responsive core for fast or slow degradation. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[49]  David A Tirrell,et al.  Core-clickable PEG-branch-azide bivalent-bottle-brush polymers by ROMP: grafting-through and clicking-to. , 2011, Journal of the American Chemical Society.

[50]  Daniel J. Burke,et al.  Applications of orthogonal "click" chemistries in the synthesis of functional soft materials. , 2009, Chemical reviews.

[51]  Jennifer L West,et al.  Thermally responsive polymer-nanoparticle composites for biomedical applications. , 2011, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[52]  B. Sumerlin,et al.  Biomedical applications of boronic acid polymers , 2011 .

[53]  Sébastien Lecommandoux,et al.  Biocompatible and biodegradable poly(trimethylene carbonate)-b-poly(L-glutamic acid) polymersomes: size control and stability. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[54]  I. Manners,et al.  Stimulus-responsive self-assembly: reversible, redox-controlled micellization of polyferrocenylsilane diblock copolymers. , 2011, Journal of the American Chemical Society.

[55]  Yiyong Mai,et al.  Self-assembly of block copolymers. , 2012, Chemical Society reviews.

[56]  Yuan Yao,et al.  Glucose-responsive vehicles containing phenylborate ester for controlled insulin release at neutral pH. , 2012, Biomacromolecules.

[57]  Min Jae Lee,et al.  Hyperbranched double hydrophilic block copolymer micelles of poly(ethylene oxide) and polyglycerol for pH-responsive drug delivery. , 2012, Biomacromolecules.

[58]  Mark E. Davis,et al.  Clinical Developments in Nanotechnology for Cancer Therapy , 2011, Pharmaceutical Research.

[59]  Christopher N. Lam,et al.  Nanopatterned Protein Films Directed by Ionic Complexation with Water-Soluble Diblock Copolymers. , 2012, Macromolecules.

[60]  T. Deming,et al.  Synthesis of polypeptides by ring-opening polymerization of α-amino acid N-carboxyanhydrides. , 2012, Topics in current chemistry.

[61]  C. Stafford,et al.  Synthesis of thiol-clickable and block copolypeptide brushes via nickel-mediated surface initiated polymerization of α-amino acid N-carboxyanhydrides (NCAs). , 2011, Chemical communications.