Polymersome carriers: from self-assembly to siRNA and protein therapeutics.

Polymersomes are polymer-based vesicular shells that form upon hydration of amphiphilic block copolymers. These high molecular weight amphiphiles impart physicochemical properties that allow polymersomes to stably encapsulate or integrate a broad range of active molecules. This robustness together with recently described mechanisms for controlled breakdown of degradable polymersomes as well as escape from endolysosomes suggests that polymersomes might be usefully viewed as having structure/property/function relationships somewhere between lipid vesicles and viral capsids. Here we summarize the assembly and development of controlled release polymersomes to encapsulate therapeutics ranging from small molecule anti-cancer drugs to siRNA and therapeutic proteins.

[1]  Lisa Pakstis,et al.  Stimuli-responsive polypeptide vesicles by conformation-specific assembly , 2004, Nature materials.

[2]  D. Papahadjopoulos,et al.  Medical applications of liposomes , 1998 .

[3]  Vladimir P. Torchilin,et al.  Biomedical aspects of drug targeting , 2002 .

[4]  F. Bates,et al.  Electromechanical limits of polymersomes. , 2001, Physical review letters.

[5]  F. Bates,et al.  From Membranes to Melts, Rouse to Reptation: Diffusion in Polymersome versus Lipid Bilayers , 2002 .

[6]  Michael L Klein,et al.  Self-assembly and properties of diblock copolymers by coarse-grain molecular dynamics , 2004, Nature materials.

[7]  Guizhi Li,et al.  Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling. , 2007, Bioconjugate chemistry.

[8]  Mathias Winterhalter,et al.  Reconstitution of Channel Proteins in (Polymerized) ABA Triblock Copolymer Membranes , 2000 .

[9]  J. Zasadzinski,et al.  Spontaneous vesicle formation in aqueous mixtures of single-tailed surfactants. , 1989, Science.

[10]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[11]  Stephan Marsch,et al.  Cell targeting by a generic receptor-targeted polymer nanocontainer platform. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[12]  Dennis E. Discher,et al.  Polymer Vesicles , 2022 .

[13]  Frank Bates,et al.  Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[14]  Xi Zhang,et al.  Reversible self-organization of a UV-responsive PEG-terminated malachite green derivative: vesicle formation and photoinduced disassembly. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[15]  Giuseppe Battaglia,et al.  Polymeric vesicle permeability: a facile chemical assay. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[16]  A. Kishimura,et al.  Encapsulation of myoglobin in PEGylated polyion complex vesicles made from a pair of oppositely charged block ionomers: a physiologically available oxygen carrier. , 2007, Angewandte Chemie.

[17]  Daniel T Kamei,et al.  Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. , 2007, Nature materials.

[18]  Xuesi Chen,et al.  Synthesis of poly(epsilon-caprolactone)-b-poly(gamma-benzyl-L-glutamic acid) block copolymer using amino organic calcium catalyst. , 2003, Biomacromolecules.

[19]  Jeffrey A Hubbell,et al.  PEG-SS-PPS: reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery. , 2007, Biomacromolecules.

[20]  Markus Antonietti,et al.  The formation of polymer vesicles or "peptosomes" by polybutadiene-block-poly(L-glutamate)s in dilute aqueous solution. , 2002, Journal of the American Chemical Society.

[21]  Carlo D. Montemagno,et al.  Protein-driven energy transduction across polymeric biomembranes , 2004 .

[22]  W. Jesse,et al.  Encapsulation of DNA by cationic diblock copolymer vesicles. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[23]  Ying Zhang,et al.  Adhesion of antibody-functionalized polymersomes. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[24]  Zhiqiang Fan,et al.  Micellar Morphologies of Poly(ε-caprolactone)-b-poly(ethylene oxide) Block Copolymers in Water with a Crystalline Core , 2007 .

[25]  F. Bates,et al.  Cryogenic Transmission Electron Microscopy (Cryo-TEM) of Micelles and Vesicles Formed in Water by Poly(ethylene oxide)-Based Block Copolymers , 2002 .

[26]  D. Hammer,et al.  Bioresorbable Vesicles Formed through Spontaneous Self-Assembly of Amphiphilic Poly(ethylene oxide)-block-polycaprolactone. , 2006, Macromolecules.

[27]  U. Seifert,et al.  Hyperviscous diblock copolymer vesicles , 2002 .

[28]  Mónica Rosa,et al.  The association of DNA and stable catanionic amino acid-based vesicles , 2007 .

[29]  Andre F Palmer,et al.  Polymersome encapsulated hemoglobin: a novel type of oxygen carrier. , 2005, Biomacromolecules.

[30]  S. Sen,et al.  Polymersome delivery of siRNA and antisense oligonucleotides. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[31]  J. M. Harris,et al.  Effect of pegylation on pharmaceuticals , 2003, Nature Reviews Drug Discovery.

[32]  Dennis E Discher,et al.  Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis-triggered controlled release vesicles. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[33]  J. Welsh,et al.  Self‐Assembled Poly(butadiene)‐b‐poly(ethylene oxide) Polymersomes as Paclitaxel Carriers , 2007, Biotechnology progress.

[34]  Eric P. Holowka,et al.  Charged polypeptide vesicles with controllable diameter. , 2005, Journal of the American Chemical Society.

[35]  Markus Antonietti,et al.  Vesicles and Liposomes: A Self‐Assembly Principle Beyond Lipids , 2003 .

[36]  S. Armes,et al.  pH-sensitive vesicles based on a biocompatible zwitterionic diblock copolymer. , 2005, Journal of the American Chemical Society.

[37]  V. Torchilin,et al.  p-Nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups. , 2001, Biochimica et biophysica acta.

[38]  Sébastien Lecommandoux,et al.  Reversible inside-out micellization of pH-responsive and water-soluble vesicles based on polypeptide diblock copolymers. , 2005, Journal of the American Chemical Society.

[39]  M J Therien,et al.  Highly conjugated, acetylenyl bridged porphyrins: new models for light-harvesting antenna systems. , 1994, Science.

[40]  Mathias Winterhalter,et al.  Nanoreactors based on (polymerized) ABA-triblock copolymer vesicles , 2000 .

[41]  K. M. Faucher,et al.  Synthesis and characterization of glycopolymer-polypeptide triblock copolymers. , 2004, Biomacromolecules.

[42]  F. Bates,et al.  Giant wormlike rubber micelles , 1999, Science.

[43]  M. Santore,et al.  The adhesion kinetics of sticky vesicles in tension: the distinction between spreading and receptor binding. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[44]  Mathias Winterhalter,et al.  Amphiphilic block copolymer nanocontainers as bioreactors , 2001 .

[45]  S. Parveen,et al.  Nanomedicine: clinical applications of polyethylene glycol conjugated proteins and drugs. , 2006, Clinical pharmacokinetics.

[46]  J. Rodríguez-Hernández,et al.  Self-assembled nanostructures from peptide-synthetic hybrid block copolymers: complex, stimuli-responsive rod-coil architectures. , 2005, Faraday discussions.

[47]  Kui Yu,et al.  Ion-Induced Morphological Changes in “Crew-Cut” Aggregates of Amphiphilic Block Copolymers , 1996, Science.

[48]  D. Discher,et al.  Visualizing worm micelle dynamics and phase transitions of a charged diblock copolymer in water. , 2005, The journal of physical chemistry. B.

[49]  Fenghua Meng,et al.  Biodegradable polymersomes as a basis for artificial cells: encapsulation, release and targeting. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[50]  A. Graff,et al.  Virus-assisted loading of polymer nanocontainer , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Najm Nico Sommerdijk,et al.  Silane-based hybrids for biomedical applications , 2002 .

[52]  Tae-Joon Jeon,et al.  Single molecule measurements of channel proteins incorporated into biomimetic polymer membranes , 2006 .

[53]  Thomas Hirt,et al.  Polymerized ABA Triblock Copolymer Vesicles , 2000 .

[54]  Reinhard Lipowsky,et al.  Dissipative particle dynamics simulations of polymersomes. , 2005, The journal of physical chemistry. B.

[55]  J. Israelachvili.  Intermolecular and surface forces , 1985 .

[56]  J. Zia,et al.  Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pH-sensitive disruption of endosomal vesicles. , 2003, The Biochemical journal.

[57]  R. Dias,et al.  Compaction and Decompaction of DNA in the Presence of Catanionic Amphiphile Mixtures , 2002 .

[58]  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 : official journal of the Controlled Release Society.

[59]  Daniel A. Hammer,et al.  Molecular Weight Dependence of Polymersome Membrane Structure, Elasticity, and Stability , 2002 .

[60]  Dexi Liu,et al.  Recognition and clearance of liposomes containing phosphatidylserine are mediated by serum opsonin. , 1995, Biochimica et biophysica acta.

[61]  K. Griebenow,et al.  Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers , 2002, The Journal of pharmacy and pharmacology.

[62]  L. Tetley,et al.  In vitro and in vivo gene transfer with poly(amino acid) vesicles. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[63]  Dennis E. Discher,et al.  Temperature‐Controlled Assembly and Release from Polymer Vesicles of Poly(ethylene oxide)‐block‐ poly(N‐isopropylacrylamide) , 2006 .

[64]  Yuting Li,et al.  Thermally responsive vesicles and their structural "locking" through polyelectrolyte complex formation. , 2006, Angewandte Chemie.

[65]  Frank S. Bates,et al.  Consequences of Nonergodicity in Aqueous Binary PEO-PB Micellar Dispersions , 2004 .

[66]  F. Bates,et al.  Polymersomes: A New Platform for Drug Targeting , 2002 .

[67]  R. Dias,et al.  DNA conformational dynamics in the presence of catanionic mixtures , 1999, FEBS letters.

[68]  J. V. D. van der Maarel,et al.  Plasmid DNA encapsulation within cationic diblock copolymer vesicles for gene delivery. , 2006, The journal of physical chemistry. B.

[69]  A. Bangham.  Liposomes: the Babraham connection. , 1993, Chemistry and physics of lipids.

[70]  Jeffrey A Hubbell,et al.  Glucose-oxidase based self-destructing polymeric vesicles. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[71]  Futian Liu,et al.  Preparation and pH triggered inversion of vesicles from poly(acrylic acid)-block-polystyrene-block-poly(4-vinyl pyridine). , 2003, Journal of the American Chemical Society.

[72]  D. Discher,et al.  Biopolymer mimicry with polymeric wormlike micelles: Molecular weight scaled flexibility, locked‐in curvature, and coexisting microphases , 2004 .

[73]  Frank Bates,et al.  Shrinkage of a rapidly growing tumor by drug-loaded polymersomes: pH-triggered release through copolymer degradation. , 2006, Molecular pharmaceutics.

[74]  M. D. Brown,et al.  Preliminary characterization of novel amino acid based polymeric vesicles as gene and drug delivery agents. , 2000, Bioconjugate chemistry.

[75]  M. Santore,et al.  Adhesion plaque formation dynamics between polymer vesicles in the limit of highly concentrated binding sites. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[76]  A. Eisenberg,et al.  Active loading and tunable release of doxorubicin from block copolymer vesicles. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[77]  Frank S Bates,et al.  On the Origins of Morphological Complexity in Block Copolymer Surfactants , 2003, Science.

[78]  F. Bates,et al.  Aqueous Dispersions of Poly(ethylene oxide)-b-poly(γ-methyl-ε-caprolactone) Block Copolymers , 2006 .

[79]  D. Discher,et al.  Hydrolytic degradation of poly(ethylene oxide)-block-polycaprolactone worm micelles. , 2005, Journal of the American Chemical Society.

[80]  M. Klein,et al.  Key roles for chain flexibility in block copolymer membranes that contain pores or make tubes. , 2005, Nano letters.

[81]  F. Bates,et al.  Polymer vesicles in vivo: correlations with PEG molecular weight. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[82]  Dennis E. Discher,et al.  Polymer vesicles : Materials science: Soft surfaces , 2002 .

[83]  D. Hammer,et al.  Polymersomes: tough vesicles made from diblock copolymers. , 1999, Science.

[84]  Vladimir P Torchilin,et al.  Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. , 2005, Advanced drug delivery reviews.

[85]  A. Kishimura,et al.  Semipermeable polymer vesicle (PICsome) self-assembled in aqueous medium from a pair of oppositely charged block copolymers: physiologically stable micro-/nanocontainers of water-soluble macromolecules. , 2006, Journal of the American Chemical Society.

[86]  T. Azzam,et al.  Biocompatible polymer vesicles from biamphiphilic triblock copolymers and their interaction with bovine serum albumin. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[87]  H. Klok,et al.  Water-soluble stimuli-responsive vesicles from peptide-based diblock copolymers. , 2002, Angewandte Chemie.

[88]  F. Bates,et al.  Preparation, stability, and in vitro performance of vesicles made with diblock copolymers. , 2000, Biotechnology and bioengineering.

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

[90]  Peter Lindner,et al.  pH-induced release from P2VP-PEO block copolymer vesicles. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[91]  L. Bell,et al.  Effect of surfactants on the physical stability of recombinant human growth hormone. , 1995, Journal of pharmaceutical sciences.

[92]  M. Klein,et al.  Simulation of Diblock Copolymer Self-Assembly, Using a Coarse-Grain Model , 2004 .

[93]  Mónica Rosa,et al.  DNA encapsulation by biocompatible catanionic vesicles. , 2007, Journal of colloid and interface science.

[94]  F. Szoka,et al.  Chemical approaches to triggerable lipid vesicles for drug and gene delivery. , 2003, Accounts of chemical research.

[95]  D. Discher,et al.  Targeted worm micelles. , 2004, Biomacromolecules.

[96]  D. Discher,et al.  Shape effects of filaments versus spherical particles in flow and drug delivery. , 2007, Nature nanotechnology.

[97]  F. Ahmed,et al.  Block Copolymer Assemblies with Cross-Link Stabilization: From Single-Component Monolayers to Bilayer Blends with PEO−PLA† , 2003 .

[98]  D. Hammer,et al.  The effect of polymer chain length and surface density on the adhesiveness of functionalized polymersomes. , 2004, Langmuir : the ACS journal of surfaces and colloids.