3-Helix micelles stabilized by polymer springs.

Despite increasing demands to employ amphiphilic micelles as nanocarriers and nanoreactors, it remains a significant challenge to simultaneously reduce the particle size and enhance the particle stability. Complementary to covalent chemical bonding and attractive intermolecular interactions, entropic repulsion can be incorporated by rational design in the headgroup of an amphiphile to generate small micelles with enhanced stability. A new family of amphiphilic peptide-polymer conjugates is presented where the hydrophilic headgroup is composed of a 3-helix coiled coil with poly(ethylene glycol) attached to the exterior of the helix bundle. When micelles form, the PEG chains are confined in close proximity and are compressed to act as a spring to generate lateral pressure. The formation of 3-helix bundles determines the location and the directionalities of the force vector of each PEG elastic spring so as to slow down amphiphile desorption. Since each component of the amphiphile can be readily tailored, these micelles provide numerous opportunities to meet current demands for organic nanocarriers with tunable stability in life science and energy science. Furthermore, present studies open new avenues to use energy arising from entropic polymer chain deformation to self-assemble energetically stable, single nanoscopic objects, much like repulsion that stabilizes bulk assemblies of colloidal particles.

[1]  Ting Xu,et al.  Long-circulating 15 nm micelles based on amphiphilic 3-helix peptide-PEG conjugates. , 2012, ACS nano.

[2]  R. Lund,et al.  Solution structural characterization of coiled-coil peptide-polymer side-conjugates. , 2012, Biomacromolecules.

[3]  Daniel K. Bonner,et al.  Enhanced stability of polymeric micelles based on postfunctionalized poly(ethylene glycol)-b-poly(γ-propargyl L-glutamate): the substituent effect. , 2012, Biomacromolecules.

[4]  Karen L Wooley,et al.  Design of polymeric nanoparticles for biomedical delivery applications. , 2012, Chemical Society reviews.

[5]  Yali Li,et al.  Degradability of poly(lactic acid)-containing nanoparticles: enzymatic access through a cross-linked shell barrier. , 2012, Journal of the American Chemical Society.

[6]  M. Uesaka,et al.  Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. , 2011, Nature nanotechnology.

[7]  M. Weck,et al.  Shell cross-linked micelle-based nanoreactors for the substrate-selective hydrolytic kinetic resolution of epoxides. , 2011, Journal of the American Chemical Society.

[8]  Shawn C. Owen,et al.  Stability of Self-Assembled Polymeric Micelles in Serum , 2011, Macromolecules.

[9]  Simon J. Holder,et al.  New micellar morphologies from amphiphilic block copolymers: disks, toroids and bicontinuous micelles , 2011 .

[10]  Badriprasad Ananthanarayanan,et al.  Thermodynamic and kinetic stability of DSPE-PEG(2000) micelles in the presence of bovine serum albumin. , 2010, The journal of physical chemistry. B.

[11]  Robert Langer,et al.  Nanotechnology in drug delivery and tissue engineering: from discovery to applications. , 2010, Nano letters.

[12]  G. Kwon,et al.  Enhanced stability of PEG-block-poly(N-hexyl stearate l-aspartamide) micelles in the presence of serum proteins. , 2010, Molecular pharmaceutics.

[13]  S Thayumanavan,et al.  Noncovalent encapsulation stabilities in supramolecular nanoassemblies. , 2010, Journal of the American Chemical Society.

[14]  Olivier Colombani,et al.  Dynamic polymeric micelles versus frozen nanoparticles formed by block copolymers , 2010 .

[15]  M. Klein,et al.  Self-Assembly of Janus Dendrimers into Uniform Dendrimersomes and Other Complex Architectures , 2010, Science.

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

[17]  F. Szoka,et al.  Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture. , 2009, Accounts of chemical research.

[18]  Erkki Ruoslahti,et al.  Targeting atherosclerosis by using modular, multifunctional micelles , 2009, Proceedings of the National Academy of Sciences.

[19]  Matthew Tirrell,et al.  Mechanisms of peptide amphiphile internalization by SJSA-1 cells in vitro. , 2009, Biochemistry.

[20]  E. Ruoslahti,et al.  Effect of the lipid chain melting transition on the stability of DSPE-PEG(2000) micelles. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[21]  W. DeGrado,et al.  New design of helix bundle peptide-polymer conjugates. , 2008, Biomacromolecules.

[22]  Kinam Park,et al.  Release of hydrophobic molecules from polymer micelles into cell membranes revealed by Förster resonance energy transfer imaging , 2008, Proceedings of the National Academy of Sciences.

[23]  H. Fan.  Nanocrystal-micelle: synthesis, self-assembly and application. , 2008, Chemical communications.

[24]  P. Low,et al.  Fast release of lipophilic agents from circulating PEG-PDLLA micelles revealed by in vivo forster resonance energy transfer imaging. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[25]  R. Zandi,et al.  Kinetic theory of virus capsid assembly , 2007, Physical biology.

[26]  Rudolf Podgornik,et al.  Role of electrostatic interactions in the assembly of empty spherical viral capsids. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[27]  F. Szoka,et al.  A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas , 2006, Proceedings of the National Academy of Sciences.

[28]  Elena E. Dormidontova,et al.  Equilibrium chain exchange kinetics of diblock copolymer micelles : Tuning and logarithmic relaxation , 2006 .

[29]  K. Matyjaszewski,et al.  Adsorption-induced scission of carbon–carbon bonds , 2006, Nature.

[30]  Francis C Szoka,et al.  Designing dendrimers for biological applications , 2005, Nature Biotechnology.

[31]  C. Hawker,et al.  Shell click-crosslinked (SCC) nanoparticles: a new methodology for synthesis and orthogonal functionalization. , 2005, Journal of the American Chemical Society.

[32]  J. L. Turner,et al.  An assessment of the effects of shell cross-linked nanoparticle size, core composition, and surface PEGylation on in vivo biodistribution. , 2005, Biomacromolecules.

[33]  Francis C Szoka,et al.  Biological evaluation of polyester dendrimer: poly(ethylene oxide) "bow-tie" hybrids with tunable molecular weight and architecture. , 2005, Molecular pharmaceutics.

[34]  W. Kegel,et al.  Competing hydrophobic and screened-coulomb interactions in hepatitis B virus capsid assembly. , 2004, Biophysical journal.

[35]  B. Schade,et al.  The first account of a structurally persistent micelle. , 2004, Angewandte Chemie.

[36]  F. Bates,et al.  Molecular Exchange in PEO−PB Micelles in Water , 2003 .

[37]  H. Klok,et al.  Advanced drug delivery devices via self-assembly of amphiphilic block copolymers. , 2001, Advanced drug delivery reviews.

[38]  K. Kataoka,et al.  Block copolymer micelles for drug delivery: design, characterization and biological significance. , 2001, Advanced drug delivery reviews.

[39]  R. Jerome,et al.  Tuning of the Exchange Dynamics of Unimers between Block Copolymer Micelles with Temperature, Cosolvents, and Cosurfactants , 2000 .

[40]  Qi Zhang,et al.  Shell Cross-Linked Nanoparticles Containing Hydrolytically Degradable, Crystalline Core Domains , 2000 .

[41]  M. Antonietti,et al.  Preparation of Palladium Colloids in Block Copolymer Micelles and Their Use for the Catalysis of the Heck Reaction , 1997 .

[42]  D. Eisenberg,et al.  The crystal structure of the designed trimeric coiled coil coil‐VaLd: Implications for engineering crystals and supramolecular assemblies , 1997, Protein science : a publication of the Protein Society.

[43]  Kazunori Kataoka,et al.  Block copolymer micelles as long-circulating drug vehicles , 1995 .

[44]  W. Mattice,et al.  Exchange of Chains between Micelles of Labeled Polystyrene-block-poly(oxyethylene) As Monitored by Nonradiative Singlet Energy Transfer , 1995 .

[45]  C. Tanford.  Macromolecules , 1994, Nature.

[46]  V. Torchilin,et al.  Biodegradable long-circulating polymeric nanospheres. , 1994, Science.

[47]  A. Eisenberg,et al.  A model of micellization for block copolymers in solutions , 1993 .

[48]  M. Teubner,et al.  Relaxation experiments in aqueous solutions of ionic micelles. 1. Theory and experiments on the system water-sodium tetradecyl sulfate-sodium perchlorate , 1981 .

[49]  J. Lang,et al.  Theory of the kinetics of micellar equilibria and quantitative interpretation of chemical relaxation studies of micellar solutions of ionic surfactants , 1976 .

[50]  E. A. G. Aniansson,et al.  Kinetics of step-wise micelle association , 1974 .

[51]  L. Willner,et al.  Equilibrium exchange kinetics in n-alkyl–PEO polymeric micelles: single exponential relaxation and chain length dependence , 2012 .

[52]  Jacob N. Israelachvili,et al.  Entropic forces between amphiphilic surfaces in liquids , 1992 .