Multifaceted polymersome platforms: Spanning from self-assembly to drug delivery and protocells

Abstract Biologically inspired self-assembly processes of amphiphilic copolymers have received an increasing attention for creating innovative and highly advanced functional materials for various biomedical applications. Polymersomes are versatile nanosystems with tremendous potential due to their increased colloidal stability, tunable membrane properties, chemical versatility, and the ability to accommodate a broad range of drugs and biomolecules. In this review, we present the principles of copolymers self-assembly and associated parameters that control the resulting self-assembled morphologies, and various methodologies developed for fabrication of polymersomes. We attempt to discuss how polymersome platforms can be applied for versatile biomedical research, from simple passive nanocarriers for drug delivery to functionalized polymersomes for active targeting approaches and advanced nanoreactors, and protocells to mimic structure and functions of biological systems.

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

[2]  Stephen Mann,et al.  Fatty acid membrane assembly on coacervate microdroplets as a step towards a hybrid protocell model. , 2014, Nature chemistry.

[3]  C. Cotman,et al.  Structure‐Activity Analyses of β‐Amyloid Peptides: Contributions of the β25–35 Region to Aggregation and Neurotoxicity , 1995 .

[4]  Hyo-Jick Choi,et al.  Artificial organelle: ATP synthesis from cellular mimetic polymersomes. , 2005, Nano letters.

[5]  F. Nudelman,et al.  Uniting polypeptides with sequence-designed peptides: synthesis and assembly of poly(gamma-benzyl L-glutamate)-b-coiled-coil peptide copolymers. , 2010, Journal of the American Chemical Society.

[6]  B. Smarsly,et al.  Bioinspired polymer vesicles based on hydrophilically modified polybutadienes , 2007 .

[7]  Stephen Mann,et al.  Systems of creation: the emergence of life from nonliving matter. , 2012, Accounts of chemical research.

[8]  Kyoung Taek Kim,et al.  Monosaccharide-responsive release of insulin from polymersomes of polyboroxole block copolymers at neutral pH. , 2012, Journal of the American Chemical Society.

[9]  S. Armes,et al.  Preparation of biocompatible zwitterionic block copolymer vesicles by direct dissolution in water and subsequent silicification within their membranes. , 2009, Langmuir : the ACS journal of surfaces and colloids.

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

[11]  J. Huwyler,et al.  Brain drug delivery of small molecules using immunoliposomes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Palmer,et al.  Biocompatible and biodegradable polymersome encapsulated hemoglobin: a potential oxygen carrier. , 2008, Bioconjugate chemistry.

[13]  Pasquale Stano,et al.  Synthetic biology of minimal living cells: primitive cell models and semi-synthetic cells , 2010, Systems and Synthetic Biology.

[14]  M. Takinoue,et al.  Droplet microfluidics for the study of artificial cells , 2011, Analytical and bioanalytical chemistry.

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

[16]  Anzar Khan,et al.  Enzyme-triggered cascade reactions and assembly of abiotic block copolymers into micellar nanostructures. , 2014, Journal of the American Chemical Society.

[17]  Nily Dan,et al.  The effect of chain length on protein solubilization in polymer-based vesicles (polymersomes). , 2003, Biophysical journal.

[18]  Annie Colin,et al.  Mastering a double emulsion in a simple co-flow microfluidic to generate complex polymersomes. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[19]  Owen Terreau,et al.  Effect of Poly(acrylic acid) Block Length Distribution on Polystyrene-b-Poly(acrylic acid) Aggregates in Solution. 1. Vesicles , 2003 .

[20]  Julie A. Theriot,et al.  Cooperative symmetry-breaking by actin polymerization in a model for cell motility , 1999, Nature Cell Biology.

[21]  Cornelia G Palivan,et al.  Can polymeric vesicles that confine enzymatic reactions act as simplified organelles? , 2011, FEBS Letters.

[22]  Win-Li Lin,et al.  Polymersomes conjugated with des-octanoyl ghrelin for the delivery of therapeutic and imaging agents into brain tissues. , 2014, Biomaterials.

[23]  Loai K. E. A. Abdelmohsen,et al.  Polymersome magneto-valves for reversible capture and release of nanoparticles , 2014, Nature Communications.

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

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

[26]  Ru Cheng,et al.  The highly efficient delivery of exogenous proteins into cells mediated by biodegradable chimaeric polymersomes. , 2010, Biomaterials.

[27]  P. Luisi.  The Emergence of Life: Autopoiesis: the logic of cellular life , 2006 .

[28]  Stephan Marsch,et al.  Toward intelligent nanosize bioreactors: a pH-switchable, channel-equipped, functional polymer nanocontainer. , 2006, Nano letters.

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

[30]  Roland Brock,et al.  Cellular integration of an enzyme-loaded polymersome nanoreactor. , 2010, Angewandte Chemie.

[31]  Ho Cheung Shum,et al.  Fabrication of polymersomes using double-emulsion templates in glass-coated stamped microfluidic devices. , 2010, Small.

[32]  W. Meier,et al.  Encapsulation of fluorescent molecules by functionalized polymeric nanocontainers: investigation by confocal fluorescence imaging and fluorescence correlation spectroscopy. , 2006, Journal of the American Chemical Society.

[33]  Wei Lu,et al.  Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Jan Steyaert,et al.  Therapeutic nanoreactors: combining chemistry and biology in a novel triblock copolymer drug delivery system. , 2005, Nano letters.

[35]  D. Taton,et al.  Synthesis of ATRP-induced dextran-b-polystyrene diblock copolymers and preliminary investigation of their self-assembly in water. , 2007, Chemical communications.

[36]  Neha P Kamat,et al.  Towards an artificial cell , 2012, FEBS letters.

[37]  Sang Hoon Han,et al.  Enhanced-throughput production of polymersomes using a parallelized capillary microfluidic device , 2013 .

[38]  A. Misra,et al.  Biomimetic doxorubicin loaded polymersomes from hyaluronan-block-poly(gamma-benzyl glutamate) copolymers. , 2009, Biomacromolecules.

[39]  Win-Li Lin,et al.  Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system. , 2014, Biomaterials.

[40]  J. Sutherland,et al.  Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions , 2009, Nature.

[41]  A. Ryan,et al.  Pathways of polymeric vesicle formation. , 2006, The journal of physical chemistry. B.

[42]  P. Wright,et al.  Polymersome production on a microfluidic platform using pH sensitive block copolymers. , 2010, Lab on a chip.

[43]  Sébastien Lecommandoux,et al.  Smart polymersomes for therapy and diagnosis: fast progress toward multifunctional biomimetic nanomedicines. , 2012, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

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

[45]  H. Wada,et al.  Prestin binding peptides as ligands for targeted polymersome mediated drug delivery to outer hair cells in the inner ear. , 2012, International journal of pharmaceutics.

[46]  N. Giuseppone,et al.  Supramolecular self-assemblies as functional nanomaterials. , 2013, Nanoscale.

[47]  Holger Schönherr,et al.  Block-copolymer vesicles as nanoreactors for enzymatic reactions. , 2009, Small.

[48]  T. Yomo,et al.  Positive roles of compartmentalization in internal reactions. , 2014, Current opinion in chemical biology.

[49]  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.

[50]  Stephen Z. D. Cheng,et al.  Self-Assembled Polystyrene-block-poly(ethylene oxide) Micelle Morphologies in Solution , 2006 .

[51]  Sébastien Lecommandoux,et al.  A simple method to achieve high doxorubicin loading in biodegradable polymersomes. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

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

[53]  T. Andresen,et al.  Polymeric nanosensors for measuring the full dynamic pH range of endosomes and lysosomes in mammalian cells. , 2009, Journal of biomedical nanotechnology.

[54]  Martin M Hanczyc,et al.  Replicating vesicles as models of primitive cell growth and division. , 2004, Current opinion in chemical biology.

[55]  W. Jiskoot,et al.  Polymersomes enhance the immunogenicity of influenza subunit vaccine , 2011 .

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

[57]  R. Nolte,et al.  Vesicles and polymerized vesicles from thiophene-containing rod-coil block copolymers. , 2003, Angewandte Chemie.

[58]  Cornelia G Palivan,et al.  Enzymatic cascade reactions inside polymeric nanocontainers: a means to combat oxidative stress. , 2011, Chemistry.

[59]  Lifeng Zhang,et al.  Crew-cut aggregates from self-assembly of blends of polystyrene-b-poly(acrylic acid) block copolymers and homopolystyrene in solution , 1999 .

[60]  Patrick Couvreur,et al.  Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. , 2013, Chemical Society reviews.

[61]  David A Weitz,et al.  Protein expression, aggregation, and triggered release from polymersomes as artificial cell-like structures. , 2012, Angewandte Chemie.

[62]  Bruno Sarmento,et al.  Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs. , 2015, ACS nano.

[63]  Françoise Brochard-Wyart,et al.  Inkjet formation of unilamellar lipid vesicles for cell-like encapsulation. , 2009, Lab on a chip.

[64]  C. Cotman,et al.  Bax Protein Expression Is Increased in Alzheimer's Brain: Correlations with DNA Damage, Bcl‐2 Expression, and Brain Pathology , 1997, Journal of neuropathology and experimental neurology.

[65]  Niklas Sandler,et al.  Microfluidic templated mesoporous silicon-solid lipid microcomposites for sustained drug delivery. , 2013, ACS applied materials & interfaces.

[66]  Hongwei Shen,et al.  Block Length Dependence of Morphological Phase Diagrams of the Ternary System of PS-b-PAA/Dioxane/H2O , 2000 .

[67]  E. Elson,et al.  Actin polymerization induces a shape change in actin-containing vesicles. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[68]  M. Mattson,et al.  beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[69]  M. Heskins,et al.  Solution Properties of Poly(N-isopropylacrylamide) , 1968 .

[70]  J. Schneider,et al.  Self-assembling materials for therapeutic delivery. , 2009, Acta biomaterialia.

[71]  Wolfgang Meier,et al.  Immobilized protein-polymer nanoreactors. , 2009, Small.

[72]  S. Armes,et al.  Preparation of primary amine-based block copolymer vesicles by direct dissolution in water and subsequent stabilization by sol-gel chemistry. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[73]  Vladimir P Torchilin,et al.  Peptide and protein drug delivery to and into tumors: challenges and solutions. , 2003, Drug discovery today.

[74]  Gregory P. Robbins,et al.  Tunable leuko-polymersomes that adhere specifically to inflammatory markers. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[75]  Jan C M van Hest,et al.  Positional assembly of enzymes in polymersome nanoreactors for cascade reactions. , 2007, Angewandte Chemie.

[76]  A. Kros,et al.  Rapid preparation of polymersomes by a water addition/solvent evaporation method , 2010 .

[77]  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.

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

[79]  Cornelia G Palivan,et al.  SOD antioxidant nanoreactors: influence of block copolymer composition on the nanoreactor efficiency. , 2010, Macromolecular bioscience.

[80]  Daniela A Wilson,et al.  Fuel concentration dependent movement of supramolecular catalytic nanomotors. , 2013, Nanoscale.

[81]  Rongqin Huang,et al.  Efficient gene delivery targeted to the brain using a transferrin-conjugated polyethyleneglycol-modified polyamidoamine dendrimer , 2007 .

[82]  Jarno Salonen,et al.  Microfluidic assisted one-step fabrication of porous silicon@acetalated dextran nanocomposites for precisely controlled combination chemotherapy. , 2015, Biomaterials.

[83]  Olivier Casse,et al.  Antioxidant nanoreactor based on superoxide dismutase encapsulated in superoxide-permeable vesicles. , 2008, The journal of physical chemistry. B.

[84]  K. Landfester,et al.  Incorporation of nanoparticles into polymersomes: size and concentration effects. , 2012, ACS nano.

[85]  J. Feijen,et al.  Biodegradable polymersomes as carriers and release systems for paclitaxel using Oregon Green® 488 labeled paclitaxel as a model compound. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[86]  S. Armes,et al.  Encapsulation of biomacromolecules within polymersomes by electroporation. , 2012, Angewandte Chemie.

[87]  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.

[88]  Chia-Chi Ho,et al.  Alternating polymervesicles. , 2008, Soft matter.

[89]  S. Hurley,et al.  Multifunctional stable and pH-responsive polymer vesicles formed by heterofunctional triblock copolymer for targeted anticancer drug delivery and ultrasensitive MR imaging. , 2010, ACS nano.

[90]  S. Mann,et al.  Membrane engineering of colloidosome microcompartments using partially hydrophobic mesoporous silica nanoparticles. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[91]  C. Palivan,et al.  Aiding nature's organelles: artificial peroxisomes play their role. , 2013, Nano letters.

[92]  Meng Zheng,et al.  Biodegradable polymersomes with an ionizable membrane: facile preparation, superior protein loading, and endosomal pH-responsive protein release. , 2012, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

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

[94]  Olivier Sandre,et al.  Recent trends in the tuning of polymersomes’ membrane properties , 2011, The European physical journal. E, Soft matter.

[95]  Jan C M van Hest,et al.  Synthetic cells and organelles: compartmentalization strategies , 2009, BioEssays : news and reviews in molecular, cellular and developmental biology.

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

[97]  Chao Deng,et al.  pH and reduction dual-bioresponsive polymersomes for efficient intracellular protein delivery. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[98]  Maïté Marguet,et al.  Cascade reactions in multicompartmentalized polymersomes. , 2014, Angewandte Chemie.

[99]  Andrew L. Schmitt,et al.  Unexpected consequences of block polydispersity on the self-assembly of ABA triblock copolymers. , 2012, Journal of the American Chemical Society.

[100]  Stephen Mann,et al.  Electrostatically gated membrane permeability in inorganic protocells. , 2015 .

[101]  M. Imperiale,et al.  A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting , 2005, Neurobiology of Disease.

[102]  J. Meadows,et al.  Propofol induced micelle formation in aqueous block copolymer solutions , 2005 .

[103]  Ho Cheung Shum,et al.  Multicompartment polymersomes from double emulsions. , 2011, Angewandte Chemie.

[104]  Stephen Mann,et al.  Designs for life: protocell models in the laboratory. , 2012, Chemical Society reviews.

[105]  K. Girish,et al.  The magic glue hyaluronan and its eraser hyaluronidase: a biological overview. , 2007, Life sciences.

[106]  Takashi Uneyama,et al.  Density functional simulation of spontaneous formation of vesicle in block copolymer solutions. , 2007, The Journal of chemical physics.

[107]  Stephen Mann,et al.  Interfacial assembly of protein–polymer nano-conjugates into stimulus-responsive biomimetic protocells , 2013, Nature Communications.

[108]  K. Zhu,et al.  Novel polymersomes based on amphiphilic graft polyphosphazenes and their encapsulation of water-soluble anti-cancer drug , 2009 .

[109]  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.

[110]  Katarzyna P. Adamala,et al.  Nonenzymatic Template-Directed RNA Synthesis Inside Model Protocells , 2013, Science.

[111]  Adam Blanazs,et al.  Self-Assembled Block Copolymer Aggregates: From Micelles to Vesicles and their Biological Applications. , 2009, Macromolecular rapid communications.

[112]  I. Pyykkö,et al.  Targeted delivery of Tet1 peptide functionalized polymersomes to the rat cochlear nerve , 2012, International journal of nanomedicine.

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

[114]  Maïté Marguet,et al.  Multicompartmentalized polymeric systems: towards biomimetic cellular structure and function. , 2013, Chemical Society reviews.

[115]  W. Meier,et al.  Ion-carrier controlled precipitation of calcium phosphate in giant ABA triblock copolymer vesicles. , 2001, Chemical communications.

[116]  Xinyuan Zhu,et al.  Self-assembly of supramolecularly engineered polymers and their biomedical applications. , 2014, Chemical communications.

[117]  Daniela A Wilson,et al.  Autonomous movement of platinum-loaded stomatocytes. , 2012, Nature chemistry.

[118]  J. Hubbell,et al.  A novel method for the encapsulation of biomolecules into polymersomes via direct hydration. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[119]  서진석,et al.  A Biodegradable Polymersome Containing Bcl-xL siRNA and Doxorubicin as a Dual Delivery Vehicle for a Synergistic Anticancer Effect , 2013 .

[120]  C. Sykes,et al.  Cell-sized liposomes that mimic cell motility and the cell cortex. , 2015, Methods in cell biology.

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

[122]  A. Patil,et al.  Design and construction of higher-order structure and function in proteinosome-based protocells. , 2014, Journal of the American Chemical Society.

[123]  Cornelia G Palivan,et al.  Protein-polymer nanoreactors for medical applications. , 2012, Chemical Society reviews.

[124]  J. Szostak,et al.  Template-directed synthesis of a genetic polymer in a model protocell , 2008, Nature.

[125]  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 .

[126]  V. Choudhary,et al.  ROP and ATRP Fabricated Dual Targeted Redox Sensitive Polymersomes Based on pPEGMA-PCL-ss-PCL-pPEGMA Triblock Copolymers for Breast Cancer Therapeutics. , 2015, ACS applied materials & interfaces.

[127]  Young-Bum Kim,et al.  Corrigendum: Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway , 2013 .

[128]  Per Linse,et al.  Monte Carlo simulations of oppositely charged macroions in solution. , 2005, The Journal of chemical physics.

[129]  Pasquale Stano,et al.  Achievements and open questions in the self-reproduction of vesicles and synthetic minimal cells. , 2010, Chemical communications.

[130]  D A Weitz,et al.  Generation of polymerosomes from double-emulsions. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[131]  J. V. van Hest,et al.  Permeability effects on the efficiency of antioxidant nanoreactors. , 2013, Biomacromolecules.

[132]  D. Discher,et al.  Visualization of degradable worm micelle breakdown in relation to drug release , 2006 .

[133]  Kensuke Kurihara,et al.  Self-reproduction of supramolecular giant vesicles combined with the amplification of encapsulated DNA. , 2011, Nature chemistry.

[134]  C. Verhoest,et al.  Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-asparaginase conjugates. , 1984, Cancer biochemistry biophysics.

[135]  Madhavan Nallani,et al.  Polymersome nanoreactors for enzymatic ring-opening polymerization. , 2007, Biomacromolecules.

[136]  D. Habault,et al.  Droplet Microfluidics to Prepare Magnetic Polymer Vesicles and to Confine the Heat in Magnetic Hyperthermia , 2012, IEEE Transactions on Magnetics.

[137]  D. Leeper,et al.  Extracellular pH distribution in human tumours. , 1995, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[138]  Athanassios Z Panagiotopoulos,et al.  Preparation of poly(ethylene glycol) protected nanoparticles with variable bioconjugate ligand density. , 2008, Biomacromolecules.

[139]  D. Weitz,et al.  Swollen vesicles and multiple emulsions from block copolymers , 2004 .

[140]  Jin Woong Kim,et al.  Multiple polymersomes for programmed release of multiple components. , 2011, Journal of the American Chemical Society.

[141]  Wolfgang Meier,et al.  Highly permeable polymeric membranes based on the incorporation of the functional water channel protein Aquaporin Z , 2007, Proceedings of the National Academy of Sciences.

[142]  Daniel A. Hammer,et al.  Molecular Weight Dependence of Polymersome Membrane Elasticity and Stability , 2001 .

[143]  A. Eisenberg,et al.  Control of Morphology through Polymer−Solvent Interactions in Crew-Cut Aggregates of Amphiphilic Block Copolymers , 1997 .

[144]  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.

[145]  I. Arends,et al.  Biocatalytic oxidation by chloroperoxidase from Caldariomyces fumago in polymersome nanoreactors. , 2009, Organic and biomolecular chemistry.

[146]  M. Ballauff,et al.  Interaction of proteins with linear polyelectrolytes and spherical polyelectrolyte brushes in aqueous solution. , 2006, Physical chemistry chemical physics : PCCP.

[147]  Sabine Van Doorslaer,et al.  A surprising system : polymeric nanoreactors containing a mimic with dual-enzyme activity , 2011 .

[148]  S. Roy,et al.  Cell-specific targeting in the mouse inner ear using nanoparticles conjugated with a neurotrophin-derived peptide ligand: potential tool for drug delivery. , 2010, International journal of pharmaceutics.

[149]  Neeraj Kumar,et al.  Development of amphotericin B loaded polymersomes based on (PEG)(3)-PLA co-polymers: Factors affecting size and in vitro evaluation. , 2010, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[150]  J. Warren,et al.  Diffuse-interface theory for structure formation and release behavior in controlled drug release systems. , 2007, Acta biomaterialia.

[151]  A. Eisenberg,et al.  Multiple Morphologies and Characteristics of “Crew-Cut” Micelle-like Aggregates of Polystyrene-b-poly(acrylic acid) Diblock Copolymers in Aqueous Solutions , 1996 .

[152]  X. Jing,et al.  Reduction and temperature dual-responsive crosslinked polymersomes for targeted intracellular protein delivery , 2011 .

[153]  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.

[154]  Mathias Winterhalter,et al.  A nanocompartment system (Synthosome) designed for biotechnological applications. , 2006, Journal of biotechnology.

[155]  Xin Huang,et al.  Synthetic cellularity based on non-lipid micro-compartments and protocell models. , 2014, Current opinion in chemical biology.

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

[157]  C. Palivan,et al.  Protein delivery: from conventional drug delivery carriers to polymeric nanoreactors , 2010, Expert opinion on drug delivery.

[158]  Christian Holtze,et al.  High throughput production of single core double emulsions in a parallelized microfluidic device. , 2012, Lab on a chip.

[159]  D. Taton,et al.  Micelles and polymersomes obtained by self-assembly of dextran and polystyrene based block copolymers. , 2009, Biomacromolecules.

[160]  T. Sugawara,et al.  Membrane dynamics of a myelin-like giant multilamellar vesicle applicable to a self-reproducing system. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[161]  Xin-guo Jiang,et al.  Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. , 2011, Bioconjugate chemistry.

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

[163]  C. Pan,et al.  Multiple Morphologies of PAA-b-PSt Assemblies throughout RAFT Dispersion Polymerization of Styrene with PAA Macro-CTA , 2011 .

[164]  Hélder A Santos,et al.  Simple Microfluidic Approach to Fabricate Monodisperse Hollow Microparticles for Multidrug Delivery. , 2015, ACS applied materials & interfaces.

[165]  J. Thévenot,et al.  Biologically active polymersomes from amphiphilic glycopeptides. , 2012, Journal of the American Chemical Society.

[166]  A. Eisenberg,et al.  Morphogenic Effect of Solvent on Crew-Cut Aggregates of Apmphiphilic Diblock Copolymers , 1998 .

[167]  Olivier Sandre,et al.  Magnetic Nanocomposite Micelles and Vesicles , 2005 .

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

[169]  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.

[170]  John Calvin Reed,et al.  Humanin peptide suppresses apoptosis by interfering with Bax activation , 2003, Nature.

[171]  Jayanth Panyam,et al.  Single-step surface functionalization of polymeric nanoparticles for targeted drug delivery. , 2009, Biomaterials.

[172]  E. Korobkova,et al.  State-resolved collisional quenching of vibrationally excited pyrazine (E(vib) = 37,900 cm(-1)) by D35Cl(v = 0). , 2005, The Journal of chemical physics.

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

[174]  M. Pitsikalis,et al.  Reversible morphological transitions of polystyrene-b-polyisoprene micelles , 2006 .

[175]  Mathias Winterhalter,et al.  Giant Free-Standing ABA Triblock Copolymer Membranes , 2000 .

[176]  Zhiyuan Zhong,et al.  Stimuli-responsive polymersomes for programmed drug delivery. , 2009, Biomacromolecules.

[177]  Giuseppe Battaglia,et al.  Polymersomes: nature inspired nanometer sized compartments , 2009 .

[178]  Stephan Marsch,et al.  Cell-specific integration of artificial organelles based on functionalized polymer vesicles. , 2008, Nano letters.

[179]  A. Eisenberg,et al.  Preparation of block copolymer vesicles in solution , 2004 .

[180]  P. Gluckman,et al.  Bax expression in mammalian neurons undergoing apoptosis, and in Alzheimer's disease hippocampus , 1997, Brain Research.

[181]  M. Gearing,et al.  Correction: Corrigendum: Tonic inhibition in dentate gyrus impairs long-term potentiation and memory in an Alzheimer’s disease model , 2014, Nature Communications.

[182]  M. Alibolandi,et al.  Synthesis and self-assembly of biodegradable polyethylene glycol-poly (lactic acid) diblock copolymers as polymersomes for preparation of sustained release system of doxorubicin , 2015, International journal of pharmaceutical investigation.

[183]  Eun Bi Choi,et al.  A biodegradable polymersome containing Bcl-xL siRNA and doxorubicin as a dual delivery vehicle for a synergistic anticancer effect. , 2013, Macromolecular bioscience.

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

[185]  Madhavan Nallani,et al.  A three-enzyme cascade reaction through positional assembly of enzymes in a polymersome nanoreactor. , 2009, Chemistry.

[186]  Neha P Kamat,et al.  Engineering Polymersome Protocells. , 2011, The journal of physical chemistry letters.

[187]  Meng Zheng,et al.  pH-sensitive degradable chimaeric polymersomes for the intracellular release of doxorubicin hydrochloride. , 2012, Biomaterials.

[188]  Tim Grundl,et al.  A review of the current understanding of redox capacity in natural, disequilibrium systems , 1994 .

[189]  Dagmar Steinhauser,et al.  Preparation of monodisperse block copolymer vesicles via flow focusing in microfluidics. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[190]  B. Toole,et al.  Hyaluronan: from extracellular glue to pericellular cue , 2004, Nature Reviews Cancer.

[191]  H. Klok,et al.  From supramolecular polymersomes to stimuli-responsive nano-capsules based on poly(diene-b-peptide) diblock copolymers , 2003, The European physical journal. E, Soft matter.

[192]  Lifeng Zhang,et al.  Morphogenic Effect of Added Ions on Crew-Cut Aggregates of Polystyrene-b-poly(acrylic acid) Block Copolymers in Solutions , 1996 .

[193]  Vladimir P. Torchilin,et al.  Accumulation of Protein-Loaded Long-Circulating Micelles and Liposomes in Subcutaneous Lewis Lung Carcinoma in Mice , 1998, Pharmaceutical Research.

[194]  F. Braet,et al.  Induced polymersome formation from a diblock PS-b-PAA polymer via encapsulation of positively charged proteins and peptides. , 2011, Chemical communications.

[195]  U. Schwaneberg,et al.  Nanocompartments with a pH release system based on an engineered OmpF channel protein , 2011 .

[196]  Dennis E Discher,et al.  Polymersome carriers: from self-assembly to siRNA and protein therapeutics. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[197]  David S. Williams,et al.  Spontaneous structuration in coacervate-based protocells by polyoxometalate-mediated membrane assembly. , 2014, Small.

[198]  M. Antognozzi,et al.  Small-molecule uptake in membrane-free peptide/nucleotide protocells , 2013 .

[199]  D. Hammer,et al.  Polymersomes: a new multi-functional tool for cancer diagnosis and therapy. , 2008, Methods.

[200]  D. Morineau,et al.  Phase separation of a binary liquid in anodic aluminium oxide templates , 2011, The European physical journal. E, Soft matter.

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

[202]  G. Robertson,et al.  Caspase-3 cleaved spectrin colocalizes with neurofilament-immunoreactive neurons in Alzheimer’s disease , 2006, Neuroscience.

[203]  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 .

[204]  G. Battaglia,et al.  Polymersomes: A Synthetic Biological Approach to Encapsulation and Delivery , 2010 .

[205]  Rongrong Hua,et al.  Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats. , 2010, Molecular pharmaceutics.

[206]  Lifeng Zhang,et al.  Structures of “crew-cut” aggregates of polystyrene-b-poly(acrylic acid) diblock copolymers , 1997 .

[207]  Monpichar Srisa-Art,et al.  Microdroplets: a sea of applications? , 2008, Lab on a chip.

[208]  Madhavan Nallani,et al.  Enzymes containing porous polymersomes as nano reaction vessels for cascade reactions. , 2008, Organic & biomolecular chemistry.

[209]  A. Misra,et al.  The in vivo behavior and antitumor activity of doxorubicin-loaded poly(γ-benzyl l-glutamate)-block-hyaluronan polymersomes in Ehrlich ascites tumor-bearing BalB/c mice. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[210]  J. Feijen,et al.  Lysosomally cleavable peptide-containing polymersomes modified with anti-EGFR antibody for systemic cancer chemotherapy. , 2011, Biomaterials.

[211]  Thomas D Pollard,et al.  Cellular Motility Driven by Assembly and Disassembly of Actin Filaments , 2003, Cell.

[212]  Ronnie Willaert,et al.  Assessment of stability, toxicity and immunogenicity of new polymeric nanoreactors for use in enzyme replacement therapy of MNGIE. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[213]  Yue Zhao,et al.  How can azobenzene block copolymer vesicles be dissociated and reformed by light? , 2005, The journal of physical chemistry. B.

[214]  P. Caliceti,et al.  Synthesis and characterization of variable conformation pH responsive block co-polymers for nucleic acid delivery and targeted cell entry , 2014 .

[215]  Fabian Itel,et al.  Polymersomes with engineered ion selective permeability as stimuli-responsive nanocompartments with preserved architecture. , 2015, Biomaterials.

[216]  Hongwei Shen,et al.  MORPHOLOGICAL PHASE DIAGRAM FOR A TERNARY SYSTEM OF BLOCK COPOLYMER PS310-B-PAA52/DIOXANE/H2O , 1999 .

[217]  D. Weitz,et al.  Microfluidic fabrication of monodisperse biocompatible and biodegradable polymersomes with controlled permeability. , 2008, Journal of the American Chemical Society.

[218]  Dong Yang,et al.  PMHDO-g-PEG Double-Bond-Based Amphiphilic Graft Copolymer: Synthesis and Diverse Self-Assembled Nanostructures , 2009 .

[219]  P. Mancini,et al.  Identification and localization of the GM1 ganglioside in the cochlea using thin-layer chromatography and cholera toxin. , 1994, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[220]  S. Mallik,et al.  Polymersome-based drug-delivery strategies for cancer therapeutics. , 2015, Therapeutic delivery.

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

[222]  S. MacNeil,et al.  Biomimetic pH Sensitive Polymersomes for Efficient DNA Encapsulation and Delivery , 2007 .

[223]  D. Bartel,et al.  Synthesizing life : Paths to unforeseeable science & technology , 2001 .

[224]  Vesa-Pekka Lehto,et al.  Microfluidic assembly of monodisperse multistage pH-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery. , 2014, Small.

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

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

[227]  L. Rizzello,et al.  Polymersomes and their applications in cancer delivery and therapy. , 2015, Nanomedicine.

[228]  W. Lu,et al.  Self-Assembled Polymersomes Conjugated with Lactoferrin as Novel Drug Carrier for Brain Delivery , 2011, Pharmaceutical Research.

[229]  Vanessa Schmidt,et al.  Nanocontainers formed by self-assembly of poly(ethylene oxide)-b-poly(glycerol monomethacrylate)-drug conjugates , 2007 .

[230]  Sebastian Seiffert,et al.  Microfluidic Synthesis of Advanced Microparticles for Encapsulation and Controlled Release{ a Introduction Lab on a Chip , 2022 .

[231]  Giuseppe Battaglia,et al.  Novel aspects of encapsulation and delivery using polymersomes. , 2014, Current opinion in pharmacology.

[232]  Afsaneh Lavasanifar,et al.  Amphiphilic block copolymers for drug delivery. , 2003, Journal of pharmaceutical sciences.

[233]  Walter Hunziker,et al.  Proteopolymersomes: in vitro production of a membrane protein in polymersome membranes. , 2011, Biointerphases.

[234]  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.

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

[236]  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.

[237]  S. MacNeil,et al.  Polymersome-mediated delivery of combination anticancer therapy to head and neck cancer cells: 2D and 3D in vitro evaluation. , 2014, Molecular pharmaceutics.

[238]  Amit Jain,et al.  The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(gamma-benzyl L-glutamate)-b-hyaluronan polymersomes. , 2010, Biomaterials.

[239]  C. Palivan,et al.  Biocompatible functionalization of polymersome surfaces: a new approach to surface immobilization and cell targeting using polymersomes. , 2011, Journal of the American Chemical Society.