Presentation on theme: "Introducing Stimuli-Responsiveness Into Polymeric Nanoparticles with"— Presentation transcript:
1David A Fulton www.dafresearchgroup.com Introducing Stimuli-Responsiveness IntoPolymeric Nanoparticles withDynamic Covalent BondsDavid A Fulton
2Polymer SynthesisLiving radical polymerizations techniques allow the synthesis of polymers with a high level of molecular precision.Polymerizations can be performed in a range of solvents, including water, and are experimentally straightforward.
3Example Polymer Synthesis with Reversible Addition-Fragmentation chain Transfer Polymerization (RAFT)Review on RAFT: G. Moad, E. Rizzardo, S. H. Thang Aust. J. Chem. 2005, 59, 669–692.Mn (GPC) = 35 kDaPDI = 1.21Mn (GPC) = 9 kDaPDI = 1.17We utilise living radical polymerization techniques to prepare polymer chains which we use as building blocks for higher-order structures.
4Polymeric Nanoparticles orlinear polymer chainsNon-covalentaggregationCovalentaggregationcore cross-linkedstar polymerssingle chainpolymer nanoparticlemicellesnanogelsMany other structures are accessible e.g. hyperbranched polymers.Sizes can be tuned to be several nm to several hundred nm.Structural precision is not as good as for dendrimers, but far easier to synthesize.
5Polymeric Nanoparticles Some applications of polymeric nanoparticles:Materials applications: adhesives, coatings, encapsulation of fragrancesBiomedical applications: drug delivery, imaging, diagnosticsPolymeric nanoparticles which are ‘smart’ can change their structures, and hence their properties, in response to stimuli and will find new applications.
6Stimuli-Responsive Polymers Some classes of polymer possess stimuli-responsive properties.They can undergo a non-linear response to an external signal e.g. a phase change.Thermoresponsive polymers are most widely studied.Poly-N-isopropylacrylamide is most widely studied thermoresponsivepolymer (Lower Critical Solution Temperature ~ 32 oC).The value of the LCST can be tuned.
7Incorporating Reversible (Dynamic) Covalent Bonds Into Polymer Assemblies Introduce ‘smart’ properties into polymeric materials by incorporation of dynamic covalent bonds INTO or BETWEEN the polymer chains.Position of equilibrium is sensitive to changes in pH, concentration and temperature.Products can undergo component exchange via trans-imination.Covalent bonds are chemically robust.Potential to kinetically fix products via imine reduction.Other well-known reversible covalent bonds are:disulfides, hydrazones, oximes
8pH- and Thermoresponsive CCS Polymers +pH = 5.5= Nile RedAlexander W. Jackson and David A. Fulton, Chem. Commun., 2011, 47, 6807 – 6809.
9pH- and Thermoresponsive Core Cross-Linked Star (CCS) Polymers = Nile RedThermoresponsive cores switch from hydrophobic to hydrophilic with changes in temperature.Alexander W. Jackson and David A. Fulton, Chem. Commun., 2011, 47, 6807 – 6809.
10Triggering Disassembly With the Simultaneous Application of Two Orthogonal Stimuli Interest in triggering events requiring the simultaneous application of multiple stimuli.pH responsiveredox responsiveProvide the opportunity to trigger events upon the simultaneous application of low pH and presence of a reductant.
11Nanoparticle Assembly Alexander Jackson and David FultonMacromolecules, 2012, In press.
12Alexander Jackson and David Fulton Macromolecules, 2012, In press. Triggering Disassembly With the Simultaneous Application of Two Orthogonal StimuliAlexander Jackson and David Fulton Macromolecules, 2012, In press.
13A Thermoresponsive Polymer Scaffold lower critical solutiontemperature can be tuned22 oC – 66 oCBenjamin S. Murray, Alexander W. Jackson, Clare Mahon, David A. FultonChem. Commun, 2010,
14A Thermally-Induced Sol-Gel Transition Daniel Whitaker and David Fultonunpublished results.gel
15SummaryLiving radical polymerization chemistry allows access to useful polymers which possess a high level of structural precision.Polymer chains can be used as building blocks to form a range of nanoparticle-like structuresIt is possible to endow polymers/polymeric assemblies with stimuli responsive properties using reversible (dynamic) covalent reactions—these systems are becoming increasingly sophisticated.Intracellular siRNA delivery (with Olaf Heidenreich, Northern Institute of Cancer Research)
16Acknowledgments Group Members: Ben Murray (now EPFL) Alex Jackson Clare MahonNiza HarunDaniel ColmanDaniel WhitakerMarta Omedes PujolMajid Al NakeebDAF group, October 2010