Skip to main content
Log in

Polymersomes as nanoreactors for preparative biocatalytic applications: current challenges and future perspectives

  • Critical Review
  • Published:
Bioprocess and Biosystems Engineering Aims and scope Submit manuscript

Abstract

Polymersomes are hollow, spherical vesicles that are surrounded by a polymer membrane. The applied polymer must be amphiphilic to promote self-assembly in aqueous solution. At the same time, the polymer composition is highly versatile, which leads to diverse properties in terms of chemical and mechanical stability, membrane permeability and the ability to functionalize the membrane. By encapsulating chemical or biological substances within the polymersomes, drug delivery systems, cell mimetics or catalytic nanoreactors can be assembled. Whereas drug delivery systems and cell mimetics based on polymersomes have been reviewed excessively, we lay focus on the current challenges and perspectives of polymersomes as nanoreactors for preparative biocatalytic applications. We discuss the importance of membrane properties for the use of polymersomes for synthetic applications and highlight advances in polymersome production and membrane functionalization. Finally, we summarize recent applications of polymersomes as nanoreactors, discuss the associated challenges and disclose future requirements and perspectives for the industrial use of polymersomes as nanoreactors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Reprinted with permission from [119]. Copyright 2014 American Chemical Society

Fig. 6

Reprinted with permission from [118]. Copyright 2013 John Wiley and Sons

Fig. 7

Reprinted with permission from [112]. Copyright 2017 American Chemical Society

Similar content being viewed by others

References

  1. Discher BM, Won YY, Ege DS, Lee JC, Bates FS, Discher DE et al (1999) Polymersomes: tough vesicles made from diblock copolymers. Science 284(5417):1143–1146

    Article  CAS  PubMed  Google Scholar 

  2. Bangham AD, Horne RW (1964) Negative staining of phospholipids + their structural modification by-surface active agents as observed in electron microscope. J Mol Biol 8(5):660

    Article  CAS  PubMed  Google Scholar 

  3. Discher DE, Eisenberg A (2002) Polymer vesicles. Science 297(5583):967–973. https://doi.org/10.1126/science.1074972

    Article  CAS  PubMed  Google Scholar 

  4. Gaitzsch J, Huang X, Voit B (2016) Engineering functional polymer capsules toward smart nanoreactors. Chem Rev 116(3):1053–1093. https://doi.org/10.1021/acs.chemrev.5b00241

    Article  CAS  PubMed  Google Scholar 

  5. Palivan CG, Goers R, Najer A, Zhang XY, Car A, Meier W (2016) Bioinspired polymer vesicles and membranes for biological and medical applications. Chem Soc Rev 45(2):377–411. https://doi.org/10.1039/c5cs00569h

    Article  CAS  PubMed  Google Scholar 

  6. Baumann P, Tanner P, Onaca O, Palivan CG (2011) Bio-decorated polymer membranes: a new approach in diagnostics and therapeutics. Polymers 3(1):173–192

    Article  CAS  Google Scholar 

  7. Elani Y, Law RV, Ces O (2014) Vesicle-based artificial cells as chemical microreactors with spatially segregated reaction pathways. Nat Commun 5:5305

    Article  CAS  PubMed  Google Scholar 

  8. Schoonen L, van Hest JCM (2016) Compartmentalization approaches in soft matter science: from nanoreactor development to organelle mimics. Adv Mater 28(6):1109–1128. https://doi.org/10.1002/adma.201502389

    Article  CAS  PubMed  Google Scholar 

  9. Langowska K, Palivan CG, Meier W (2013) Polymer nanoreactors shown to produce and release antibiotics locally. Chem Commun (Camb) 49(2):128–130. https://doi.org/10.1039/c2cc36345c

    Article  CAS  Google Scholar 

  10. Onaca O, Hughes DW, Balasubramanian V, Grzelakowski M, Meier W, Palivan CG (2010) SOD antioxidant nanoreactors: influence of block copolymer composition on the nanoreactor efficiency. Macromol Biosci 10(5):531–538. https://doi.org/10.1002/mabi.200900379

    Article  CAS  PubMed  Google Scholar 

  11. Axthelm F, Casse O, Koppenol WH, Nauser T, Meier W, Palivan CG (2008) Antioxidant nanoreactor based on superoxide dismutase encapsulated in superoxide-permeable vesicles. J Phys Chem B 112(28):8211–8217

    Article  CAS  PubMed  Google Scholar 

  12. Louzao I, van Hest JCM (2013) Permeability effects on the efficiency of antioxidant nanoreactors. Biomacromol 14(7):2364–2372. https://doi.org/10.1021/bm400493b

    Article  CAS  Google Scholar 

  13. Tanner P, Onaca O, Balasubramanian V, Meier W, Palivan CG (2011) Enzymatic cascade reactions inside polymeric nanocontainers: a means to combat oxidative stress. Chem Eur J 17(16):4552–4560

    Article  CAS  PubMed  Google Scholar 

  14. Meeuwissen SA, Rioz-Martinez A, de Gonzalo G, Fraaije MW, Gotor V, van Hest JCM (2011) Cofactor regeneration in polymersome nanoreactors: enzymatically catalysed Baeyer–Villiger reactions. J Mater Chem 21(47):18923–18926

    Article  CAS  Google Scholar 

  15. LoPresti C, Lomas H, Massignani M, Smart T, Battaglia G (2009) Polymersomes: nature inspired nanometer sized compartments. J Mater Chem 19(22):3576–3590

    Article  CAS  Google Scholar 

  16. Napoli A, Tirelli N, Wehrli E, Hubbell JA (2002) Lyotropic behavior in water of amphiphilic ABA triblock copolymers based on poly(propylene sulfide) and poly(ethylene glycol). Langmuir 18(22):8324–8329

    Article  CAS  Google Scholar 

  17. Itel F, Chami M, Najer A, Lorcher S, Wu DL, Dinu IA et al (2014) Molecular organization and dynamics in polymersome membranes: a lateral diffusion study. Macromolecules 47(21):7588–7596

    Article  CAS  Google Scholar 

  18. Battaglia G, Ryan AJ (2005) Bilayers and interdigitation in block copolymer vesicles. J Am Chem Soc 127(24):8757–8764. https://doi.org/10.1021/ja050742y

    Article  CAS  PubMed  Google Scholar 

  19. Chen Q, Schonherr H, Vancso GJ (2009) Mechanical properties of block copolymer vesicle membranes by atomic force microscopy. Soft Matter 5(24):4944–4950. https://doi.org/10.1039/b903110c

    Article  CAS  Google Scholar 

  20. Le Meins JF, Sandre O, Lecommandoux S (2011) Recent trends in the tuning of polymersomes’ membrane properties. Eur Phys J E Soft Mater 34(2):1–17. https://doi.org/10.1140/epje/i2011-11014-y

    Article  CAS  Google Scholar 

  21. Srinivas G, Discher DE, Klein ML (2004) Self-assembly and properties of diblock copolymers by coarse-grain molecular dynamics. Nat Mater 3(9):638–644. https://doi.org/10.1038/nmat1185

    Article  CAS  PubMed  Google Scholar 

  22. Bates FS, Fredrickson GH (1990) Block copolymer thermodynamics—theory and experiment. Annu Rev Phys Chem 41:525–557

    Article  CAS  PubMed  Google Scholar 

  23. Battaglia G, Ryan AJ, Tomas S (2006) Polymeric vesicle permeability: a facile chemical assay. Langmuir 22(11):4910–4913. https://doi.org/10.1021/la060354p

    Article  CAS  PubMed  Google Scholar 

  24. Carlsen A, Glaser N, Le Meins JF, Lecommandoux S (2011) Block copolymer vesicle permeability measured by osmotic swelling and shrinking. Langmuir 27(8):4884–4890

    Article  CAS  PubMed  Google Scholar 

  25. Kumar M, Grzelakowski M, Zilles J, Clark M, Meier W (2007) Highly permeable polymeric membranes based on the incorporation of the functional water channel protein Aquaporin Z. Proc Natl Acad Sci 104(52):20719–20724. https://doi.org/10.1073/pnas.0708762104

    Article  PubMed  Google Scholar 

  26. Grzelakowski M, Cherenet MF, Shen YX, Kumar M (2015) A framework for accurate evaluation of the promise of aquaporin based biomimetic membranes. J Membr Sci 479:223–231

    Article  CAS  Google Scholar 

  27. Mathai JC, Tristram-Nagle S, Nagle JF, Zeidel ML (2008) structural determinants of water permeability through the lipid membrane. J Gen Physiol 131(1):69–76. https://doi.org/10.1085/jgp.200709848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Leson A, Filiz V, Forster S, Mayer C (2007) Water permeation through block-copolymer vesicle membranes. Chem Phys Lett 444(4–6):268–72

    Article  CAS  Google Scholar 

  29. Leson A, Hauschild S, Rank A, Neub A, Schubert R, Forster S et al (2007) Molecular exchange through membranes of poly(2-vinylpyridine-block-ethylene oxide) vesicles. Small 3(6):1074–1083. doi:https://doi.org/10.1002/smll.200600540

    Article  CAS  PubMed  Google Scholar 

  30. Rumplecker A, Forster A, Zahres M, Mayer C (2004) Molecular exchange through vesicle membranes: a pulsed field gradient nuclear magnetic resonance study. J Chem Phys 120(18):8740–8747

    Article  CAS  PubMed  Google Scholar 

  31. Bauer A, Hauschild S, Stolzenburg M, Forster S, Mayer C (2006) Molecular exchange through membranes of poly(2-vinylpyridine-block-ethylene oxide) vesicles. Chem Phys Lett 419(4–6):430–433

    Article  CAS  Google Scholar 

  32. Poschenrieder ST, Klermund L, Langer B, Castiglione K (2017) Determination of permeability coefficients of polymersomal membranes for hydrophilic molecules. Langmuir 33(24):6011–6020. https://doi.org/10.1021/acs.langmuir.6b04598

    Article  CAS  PubMed  Google Scholar 

  33. Bermudez H, Brannan AK, Hammer DA, Bates FS, Discher DE (2002) Molecular weight dependence of polymersome membrane structure, elasticity, and stability. Macromolecules 35(21):8203–8208. https://doi.org/10.1021/ma020669l

    Article  CAS  Google Scholar 

  34. Lee JCM, Bermudez H, Discher BM, Sheehan MA, Won YY, Bates FS et al (2001) Preparation, stability, and in vitro performance of vesicles made with diblock copolymers. Biotechnol Bioeng 73(2):135–145. https://doi.org/10.1002/bit.1045

    Article  CAS  PubMed  Google Scholar 

  35. Iyisan B, Janke A, Reichenbach P, Eng LM, Appelhans D, Voit B (2016) Immobilized multifunctional polymersomes on solid surfaces: infrared light-induced selective photochemical reactions, pH responsive behavior, and probing mechanical properties under liquid phase. ACS Appl Mater Int 8(24):15788–15801

    Article  CAS  Google Scholar 

  36. Longo ML, Ly HV (2007) Micropipet aspiration for measuring elastic properties of lipid bilayers. Methods Mol Biol 400:421–437. https://doi.org/10.1007/978-1-59745-519-0_28

    Article  CAS  PubMed  Google Scholar 

  37. Li SL, Byrne B, Welsh J, Palmer AF (2007) Self-assembled poly(butadiene)-b-poly(ethylene oxide) polymersomes as paclitaxel carriers. Biotechnol Progr 23(1):278–285

    Article  Google Scholar 

  38. Poschenrieder ST, Wagner SG, Castiglione K (2016) Efficient production of uniform nanometer-sized polymer vesicles in stirred-tank reactors. J Appl Polym Sci. https://doi.org/10.1002/app.43274

    Article  Google Scholar 

  39. Stitt EH (2002) Alternative multiphase reactors for fine chemicals—a world beyond stirred tanks? Chem Eng J 90(1–2):47–60

    Article  CAS  Google Scholar 

  40. Henzler HJ, Biedermann A (1996) Model studies on particle stress in reactors. Chem Ing Tech 68(12):1546–1561. https://doi.org/10.1002/cite.330681205

    Article  CAS  Google Scholar 

  41. Henzler HJ (2000) Particle Stress in Bioreactors. In: Schügerl K, Kretzmer G, Henzler HJ, Kieran PM, Kretzmer G, MacLoughlin PE et al (eds) Advances in biochemical engineering/biotechnology. Springer, Berlin, pp 35–82

    Google Scholar 

  42. Weuster-Botz D (2007) Process intensification of whole-cell biocatalysis with ionic liquids. Chem Rec 7(6):334–340

    Article  CAS  PubMed  Google Scholar 

  43. Castiglione K, Fu YL, Polte I, Leupold S, Meo A, Weuster-Botz D (2017) Asymmetric whole-cell bioreduction of (R)-carvone by recombinant Escherichia coli with in situ substrate supply and product removal. Biochem Eng J 117:102–111

    Article  CAS  Google Scholar 

  44. Peters M, Zavrel M, Kahlen J, Schmidt T, Ansorge-Schurnacher M, Leitner W et al (2008) Systematic approach to solvent selection for biphasic systems with a combination of COSMO-RS and a dynamic modeling tool. Eng Life Sci 8(5):546–552

    Article  CAS  Google Scholar 

  45. Eckstein MF, Lembrecht J, Schumacher J, Eberhard W, Spiess AC, Peters M et al (2006) Maximise equilibrium conversion in biphasic catalysed reactions: how to obtain reliable data for equilibrium constants? Adv Synth Catal 348(12–13):1597–1604

    Article  CAS  Google Scholar 

  46. Bräutigam S, Dennewald D, Schürmann M, Lutje-Spelberg J, Pitner W-R, Weuster-Botz D (2009) Whole-cell biocatalysis: evaluation of new hydrophobic ionic liquids for efficient asymmetric reduction of prochiral ketones. Enzyme Microbiol Technol 45(4):310–316. https://doi.org/10.1016/j.enzmictec.2009.06.015

    Article  CAS  Google Scholar 

  47. van Rantwijk F, Sheldon RA (2007) Biocatalysis in ionic liquids. Chem Rev 107(6):2757–2785. https://doi.org/10.1021/cr050946x

    Article  CAS  PubMed  Google Scholar 

  48. Dennewald D, Pitner WR, Weuster-Botz D (2011) Recycling of the ionic liquid phase in process integrated biphasic whole-cell biocatalysis. Process Biochem 46(5):1132–1137

    Article  CAS  Google Scholar 

  49. Matsuda T (2013) Recent progress in biocatalysis using supercritical carbon dioxide. J Biosci Bioeng 115(3):233–241

    Article  CAS  PubMed  Google Scholar 

  50. Yoon SH, Lee EG, Das A, Lee SH, Li C, Ryu HK et al (2007) Enhanced vanillin production from recombinant E. coli using NTG mutagenesis and adsorbent resin. Biotechnol Prog 23(5):1143–1148

    PubMed  Google Scholar 

  51. Phillips T, Chase M, Wagner S, Renzi C, Powell M, DeAngelo J et al (2013) Use of in situ solid-phase adsorption in microbial natural product fermentation development. J Ind Microbiol Biotechnol 40(5):411–425. https://doi.org/10.1007/s10295-013-1247-9

    Article  CAS  PubMed  Google Scholar 

  52. Nardin C, Thoeni S, Widmer J, Winterhalter M, Meier W (2000) Nanoreactors based on (polymerized) ABA-triblock copolymer vesicles. Chem Commun (15):1433–1434

  53. Nardin C, Hirt T, Leukel J, Meier W (2000) Polymerized ABA triblock copolymer vesicles. Langmuir 16(3):1035–1041. doi:https://doi.org/10.1021/la990951u

    Article  CAS  Google Scholar 

  54. Nardin C, Meier WG (2001) Polymerizable amphiphilic block copolymers: from nanostructured hydrogels to nanoreactors and ultrathin films. Chimia 55(3):142–146

    CAS  Google Scholar 

  55. Gräfe D, Gaitzsch J, Appelhans D, Voit B (2014) Cross-linked polymersomes as nanoreactors for controlled and stabilized single and cascade enzymatic reactions. Nanoscale 6(18):10752–10761. https://doi.org/10.1039/c4nr02155j

    Article  PubMed  Google Scholar 

  56. Discher BM, Bermudez H, Hammer DA, Discher DE, Won YY, Bates FS (2002) Cross-linked polymersome membranes: vesicles with broadly adjustable properties. J Phys Chem B 106(11):2848–2854

    Article  CAS  Google Scholar 

  57. Gaitzsch J, Appelhans D, Wang LG, Battaglia G, Voit B (2012) Synthetic bio-nanoreactor: mechanical and chemical control of polymersome membrane permeability. Angew Chem Int Ed 51(18):4448–4451

    Article  CAS  Google Scholar 

  58. Gaitzsch J, Appelhans D, Grafe D, Schwille P, Voit B (2011) Photo-crosslinked and pH sensitive polymersomes for triggering the loading and release of cargo. Chem Commun 47(12):3466–3468

    Article  CAS  Google Scholar 

  59. Xu HF, Meng FH, Zhong ZY (2009) Reversibly crosslinked temperature-responsive nano-sized polymersomes: synthesis and triggered drug release. J Mater Chem 19(24):4183–4190

    Article  CAS  Google Scholar 

  60. Liu XF, Yaszemski MJ, Lu LC (2016) Expansile crosslinked polymersomes for pH sensitive delivery of doxorubicin. Biomater Sci UK 4(2):245–249

    Article  CAS  Google Scholar 

  61. Hales M, Barner-Kowollik C, Davis TP, Stenzel MH (2004) Shell-cross-linked vesicles synthesized from block copolymers of poly(d,l-lactide) and poly (N-isopropyl acrylamide) as thermoresponsive nanocontainers. Langmuir 20(25):10809–10817

    Article  CAS  PubMed  Google Scholar 

  62. Wang ZP, van Oers MCM, Rutjes FPJT., van Hest JCM (2012) Polymersome colloidosomes for enzyme catalysis in a biphasic system. Angew Chem Int Ed 51(43):10746–10750. https://doi.org/10.1002/anie.201206555

    Article  CAS  Google Scholar 

  63. Wang ZP, van Oers MCM, van Hest JCM, Rutjes FPJT. (2014) Polymersome pickering emulsion for enzyme catalysis in a biphasic system. Abstr Pap Am Chem Soc 247

  64. Battaglia G, Ryan AJ (2006) Pathways of polymeric vesicle formation. J Phys Chem B 110(21):10272–10279. https://doi.org/10.1021/jp060728n

    Article  CAS  PubMed  Google Scholar 

  65. Ahmed F, Discher DE (2004) Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis-triggered controlled release vesicles. J Control Release 96(1):37–53

    Article  CAS  PubMed  Google Scholar 

  66. Meeuwissen SA, Kim KT, Chen YC, Pochan DJ, van Hest JCM (2011) Controlled shape transformation of polymersome stomatocytes. Angew Chem Int Ed 50(31):7070–7073

    Article  CAS  Google Scholar 

  67. Schild HG (1992) Poly (N-Isopropylacrylamide)—experiment, theory and application. Prog Polym Sci 17(2):163–249

    Article  CAS  Google Scholar 

  68. Pelton R (2010) Poly(N-isopropylacrylamide) (PNIPAM) is never hydrophobic. J Colloid Interf Sci 348(2):673–674

    Article  CAS  Google Scholar 

  69. Pramanik P, Ghosh S (2015) Thermoresponsive polymersome from a double hydrophilic block copolymer. J Polym Sci Pol Chem 53(21):2444–2451

    Article  CAS  Google Scholar 

  70. Lomas H, Canton I, MacNeil S, Du J, Armes SP, Ryan AJ et al (2007) Biomimetic pH sensitive polymersomes for efficient DNA encapsulation and delivery. Adv Mater 19(23):4238-+

    Article  CAS  Google Scholar 

  71. Yassin MA, Appelhans D, Mendes RG, Rummeli MH, Voit B (2012) pH-dependent release of doxorubicin from fast photo-cross-linkable polymersomes based on benzophenone units. Chem Eur J 18(39):12227–12231

    Article  CAS  PubMed  Google Scholar 

  72. Kim I, Lee NE, Jeong YJ, Chung YH, Cho BK, Lee E (2014) Micellar and vesicular nanoassemblies of triazole-based amphiphilic probes triggered by mercury(II) ions in a 100% aqueous medium. Chem Commun 50(90):14006–14009

    Article  CAS  Google Scholar 

  73. Hauschild S, Lipprandt U, Rumplecker A, Borchert U, Rank A, Schubert R et al (2005) Direct preparation and loading of lipid and polymer vesicles using inkjets. Small 1(12):1177–1180. https://doi.org/10.1002/smll.200500093

    Article  CAS  PubMed  Google Scholar 

  74. Thiele J, Steinhauser D, Pfohl T, Forster S (2010) Preparation of monodisperse block copolymer vesicles via flow focusing in microfluidics. Langmuir 26(9):6860–6863. https://doi.org/10.1021/la904163v

    Article  CAS  PubMed  Google Scholar 

  75. Thiele J, Abate AR, Shum HC, Bachtler S, Forster S, Weitz DA (2010) Fabrication of polymersomes using double-emulsion templates in glass-coated stamped microfluidic devices. Small 6(16):1723–1727. https://doi.org/10.1002/smll.201000798

    Article  CAS  PubMed  Google Scholar 

  76. Thiele J, Chokkalingam V, Ma SH, Wilson DA, Huck WTS (2014) Vesicle budding from polymersomes templated by microfluidically prepared double emulsions. Mater Horizons 1(1):96–101. https://doi.org/10.1039/c3mh00043e

    Article  CAS  Google Scholar 

  77. Brown L, McArthur SL, Wright PC, Lewis A, Battaglia G (2010) Polymersome production on a microfluidic platform using pH sensitive block copolymers. Lab Chip 10(15):1922–1928. doi:https://doi.org/10.1039/C004036c

    Article  CAS  PubMed  Google Scholar 

  78. Thiermann R, Mueller W, Montesinos-Castellanos A, Metzke D, Löb P, Hessel V et al (2012) Size controlled polymersomes by continuous self-assembly in micromixers. Polymer 53(11):2205–2210. https://doi.org/10.1016/j.polymer.2012.03.058

    Article  CAS  Google Scholar 

  79. Bleul R, Thiermann R, Marten GU, House MJ, Pierre TGS, Häfeli UO et al (2013) Continuously manufactured magnetic polymersomes–a versatile tool (not only) for targeted cancer therapy. Nanoscale 5(23):11385. https://doi.org/10.1039/c3nr02190d

    Article  CAS  PubMed  Google Scholar 

  80. Poschenrieder ST, Schiebel SK, Castiglione K (2017) Polymersomes for biotechnological applications: Large-scale production of nano-scale vesicles. Eng Life Sci 17(1):58–70. https://doi.org/10.1002/elsc.201600100

    Article  CAS  Google Scholar 

  81. Du J, Tang Y, Lewis AL, Armes SP (2005) pH-sensitive vesicles based on a biocompatible zwitterionic diblock copolymer. J Am Chem Soc 127(51):17982–17983. https://doi.org/10.1021/ja056514l

    Article  CAS  PubMed  Google Scholar 

  82. Wang LG, Chierico L, Little D, Patikarnmonthon N, Yang Z, Azzouz M et al (2012) Encapsulation of biomacromolecules within polymersomes by electroporation. Angew Chem Int Ed 51(44):11122–11125. https://doi.org/10.1002/anie.201204169

    Article  CAS  Google Scholar 

  83. van Dongen SFM, Nallani M, Cornelissen JLLM., Nolte RJM, van Hest JCM (2009) A three-enzyme cascade reaction through positional assembly of enzymes in a polymersome nanoreactor. Chem Eur J 15(5):1107–1114

    Article  CAS  PubMed  Google Scholar 

  84. Vriezema DM, Garcia PM, Sancho Oltra N, Hatzakis NS, Kuiper SM, Nolte RJ et al (2007) Positional assembly of enzymes in polymersome nanoreactors for cascade reactions. Angew Chem Int Ed 46(39):7378–7382. https://doi.org/10.1002/anie.200701125

    Article  CAS  Google Scholar 

  85. Vijayan K, Discher DE, Lal J, Janmey P, Goulian M (2005) Interactions of membrane-active peptides with thick, neutral, nonzwitterionic bilayers. J Phys Chem B 109(30):14356–14364. https://doi.org/10.1021/jp050060x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Gonzalez-Perez A, Stibius KB, Vissing T, Nielsen CH, Mouritsen OG (2009) Biomimetic triblock copolymer membrane arrays: a stable template for functional membrane proteins. Langmuir 25(18):10447–10450. https://doi.org/10.1021/la902417m

    Article  CAS  PubMed  Google Scholar 

  87. Stoenescu R, Graff A, Meier W (2004) Asymmetric ABC-triblock copolymer membranes induce a directed insertion of membrane proteins. Macromol Biosci 4(10):930–935. https://doi.org/10.1002/mabi.200400065

    Article  CAS  PubMed  Google Scholar 

  88. Itel F, Najer A, Palivan CG, Meier W (2015) Dynamics of membrane proteins within synthetic polymer membranes with large hydrophobic mismatch. Nano Lett 15(6):3871–3878. https://doi.org/10.1021/acs.nanolett.5b00699

    Article  CAS  PubMed  Google Scholar 

  89. Srinivas G, Discher DE, Klein ML (2005) Key roles for chain flexibility in block copolymer membranes that contain pores or make tubes. Nano Lett 5(12):2343–2349

    Article  CAS  PubMed  Google Scholar 

  90. Kumar M, Habel JE, Shen YX, Meier WP, Walz T (2012) High-density reconstitution of functional water channels into vesicular and planar block copolymer membranes. J Am Chem Soc 134(45):18631–18637. https://doi.org/10.1021/ja304721r

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Nallani M, Andreasson-Ochsner M, Tan CW, Sinner EK, Wisantoso Y, Geifman-Shochat S et al (2011) Proteopolymersomes: in vitro production of a membrane protein in polymersome membranes. Biointerphases 6(4):153–157. https://doi.org/10.1116/1.3644384

    Article  CAS  PubMed  Google Scholar 

  92. Muhammad N, Dworeck T, Fioroni M, Schwaneberg U (2011) Engineering of the E. coli outer membrane protein FhuA to overcome the hydrophobic mismatch in thick polymeric membranes. J Nanobiotechnol 9:8. https://doi.org/10.1186/1477-3155-9-8

    Article  CAS  Google Scholar 

  93. Opsteen JA, Brinkhuis RP, Teeuwen RL, Lowik DW, van Hest JC (2007) “Clickable” polymersomes. Chem Commun (Camb) (30):3136–3138. https://doi.org/10.1039/b704568a

  94. Debets MF, Leenders WP, Verrijp K, Zonjee M, Meeuwissen SA, Otte-Holler I et al (2013) Nanobody-functionalized polymersomes for tumor-vessel targeting. Macromol Biosci 13(7):938–945. https://doi.org/10.1002/mabi.201300039

    Article  CAS  PubMed  Google Scholar 

  95. van Dongen SFM, Nallani M, Schoffelen S, Cornelissen JJLM., Nolte RJM, van Hest JCM (2008) A block copolymer for functionalisation of polymersome surfaces. Macromol Rapid Commun 29(4):321–325

    Article  CAS  Google Scholar 

  96. Domes S, Filiz V, Nitsche J, Fromsdorf A, Forster S (2010) Covalent attachment of polymersomes to surfaces. Langmuir 26(10):6927–6931. https://doi.org/10.1021/la904175u

    Article  CAS  PubMed  Google Scholar 

  97. Petersen MA, Yin LG, Kokkoli E, Hillmyer MA (2010) Synthesis and characterization of reactive PEO-PMCL polymersomes. Polymer Chem 1(8):1281–1290. https://doi.org/10.1039/c0py00143k

    Article  CAS  Google Scholar 

  98. Egli S, Nussbaumer MG, Balasubramanian V, Chami M, Bruns N, Palivan C et al (2011) Biocompatible functionalization of polymersome surfaces: a new approach to surface immobilization and cell targeting using polymersomes. J Am Chem Soc 133(12):4476–4483. https://doi.org/10.1021/ja110275f

    Article  CAS  PubMed  Google Scholar 

  99. Christian NA, Milone MC, Ranka SS, Li GZ, Frail PR, Davis KP et al (2007) Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling. Bioconjug Chem 18(1):31–40

    Article  CAS  PubMed  Google Scholar 

  100. Pang Z, Lu W, Gao H, Hu K, Chen J, Zhang C et al (2008) Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26. J Control Release 128(2):120–127. https://doi.org/10.1016/j.jconrel.2008.03.007

    Article  CAS  PubMed  Google Scholar 

  101. Broz P, Benito SM, Saw C, Burger P, Heider H, Pfisterer M et al (2005) Cell targeting by a generic receptor-targeted polymer nanocontainer platform. J Control Release 102(2):475–488. https://doi.org/10.1016/j.jconrel.2004.10.014

    Article  CAS  PubMed  Google Scholar 

  102. Grzelakowski M, Onaca O, Rigler P, Kumar M, Meier W (2009) Immobilized protein–polymer nanoreactors. Small 5(22):2545–2548. https://doi.org/10.1002/smll.200900603

    Article  CAS  PubMed  Google Scholar 

  103. Lin JJ, Ghoroghchian P, Zhang Y, Hammer DA (2006) Adhesion of antibody-functionalized polymersomes. Langmuir 22(9):3975–3979. https://doi.org/10.1021/la052445c

    Article  CAS  PubMed  Google Scholar 

  104. Lin JJ, Silas JA, Bermudez H, Milam VT, Bates FS, Hammer DA (2004) The effect of polymer chain length and surface density on the adhesiveness of functionalized polymersomes. Langmuir 20(13):5493–5500

    Article  CAS  PubMed  Google Scholar 

  105. Rigler P, Meier W (2006) Encapsulation of fluorescent molecules by functionalized polymeric nanocontainers: Investigation by confocal fluorescence imaging and fluorescence correlation Spectroscopy. J Am Chem Soc 128(1):367–373

    Article  CAS  PubMed  Google Scholar 

  106. Felici M, Marza-Perez M, Hatzakis NS, Nolte RJ, Feiters MC (2008) Beta-cyclodextrin-appended giant amphiphile: aggregation to vesicle polymersomes and immobilisation of enzymes. Chemistry 14(32):9914–9920. https://doi.org/10.1002/chem.200801429

    Article  CAS  PubMed  Google Scholar 

  107. Guo M, Jiang M, Zhang G (2008) Surface modification of polymeric vesicles via host-guest inclusion complexation. Langmuir 24(19):10583–10586. https://doi.org/10.1021/la802126w

    Article  CAS  PubMed  Google Scholar 

  108. Nehring R, Palivan CG, Moreno-Flores S, Mantion A, Tanner P, Toca-Herrera JL et al (2010) Protein decorated membranes by specific molecular interactions. Soft Mater 6(12):2815–2824

    Article  CAS  Google Scholar 

  109. Nehring R, Palivan CG, Casse O, Tanner P, Tuxen J, Meier W (2009) Amphiphilic diblock copolymers for molecular recognition: metal-nitrilotriacetic acid functionalized vesicles. Langmuir 25(2):1122–1130. https://doi.org/10.1021/la8027308

    Article  CAS  PubMed  Google Scholar 

  110. Noor M, Dworeck T, Schenk A, Shinde P, Fioroni M, Schwaneberg U (2012) Polymersome surface decoration by an EGFP fusion protein employing Cecropin A as peptide “anchor”. J Biotechnol 157(1):31–37. https://doi.org/10.1016/j.jbiotec.2011.10.005

    Article  CAS  PubMed  Google Scholar 

  111. Klermund L, Poschenrieder ST, Castiglione K (2016) Simple surface functionalization of polymersomes using non-antibacterial peptide anchors. J Nanobiotechnol 14:48. https://doi.org/10.1186/s12951-016-0205-x

    Article  CAS  Google Scholar 

  112. Klermund L, Poschenrieder ST, Castiglione K (2017) Biocatalysis in polymersomes: improving multienzyme cascades with incompatible reaction steps by compartmentalization. ACS Catal 7(6):3900–3904. https://doi.org/10.1021/acscatal.7b00776

    Article  CAS  Google Scholar 

  113. Schmidt S, Castiglione K, Kourist R (2017) Overcoming the incompatibility challenge in chemoenzymatic and multi-catalytic cascade reactions. Chemistry. https://doi.org/10.1002/chem.201703353

    Article  PubMed  PubMed Central  Google Scholar 

  114. Ge J, Lu DN, Liu ZX, Liu Z (2009) Recent advances in nanostructured biocatalysts. Biochem Eng J 44(1):53–59. https://doi.org/10.1016/j.bej.2009.01.002

    Article  CAS  Google Scholar 

  115. Zhang YF, Hess H (2017) Toward rational design of high-efficiency enzyme cascades. ACS Catal 7(9):6018–6027. https://doi.org/10.1021/acscatal.7b01766

    Article  CAS  Google Scholar 

  116. Poschenrieder ST, Schiebel SK, Castiglione K (2017) Stability of polymersomes with focus on their use as nanoreactors. Eng Life Sci. https://doi.org/10.1002/elsc.201700009

    Article  Google Scholar 

  117. Siti W, de Hoog HPM, Fischer O, Shan WY, Tomczak N, Nallani M et al (2014) An intercompartmental enzymatic cascade reaction in channel-equipped polymersome-in-polymersome architectures. J Mater Chem B 2(18):2733–2737. https://doi.org/10.1039/c3tb21849j

    Article  CAS  Google Scholar 

  118. Peters RJRW., Marguet M, Marais S, Fraaije MW, van Hest JCM, Lecommandoux S (2014) Cascade reactions in multicompartmentalized polymersomes. Angew Chem Int Ed 53(1):146–150. https://doi.org/10.1002/anie.201308141

    Article  CAS  Google Scholar 

  119. Spulber M, Baumann P, Saxer SS, Pieles U, Meier W, Bruns N (2014) Poly(N-vinylpyrrolidone)-poly(dimethylsiloxane)-based polymersome nanoreactors for laccase-catalyzed biotransformations. Biomacromol 15(4):1469–1475. https://doi.org/10.1021/bm500081j

    Article  CAS  Google Scholar 

  120. Kim KT, Cornelissen JJLM., Nolte RJM, van Hest JCM (2009) A polymersome nanoreactor with controllable permeability induced by stimuli-responsive block copolymers. Adv Mater 21(27):2787–2791. https://doi.org/10.1002/adma.200900300

    Article  CAS  Google Scholar 

  121. de Hoog HM, Nallani M, Cornelissen JJ, Rowan AE, Nolte RJ, Arends IW (2009) Biocatalytic oxidation by chloroperoxidase from Caldariomyces fumago in polymersome nanoreactors. Org Biomol Chem 7(22):4604–4610. https://doi.org/10.1039/b911370c

    Article  CAS  PubMed  Google Scholar 

  122. Schmitt C, Lippert AH, Bonakdar N, Sandoghdar V, Voll LM (2016) Compartmentalization and transport in synthetic vesicles. Front Bioeng Biotechnol 4(19):1–12 doi:Journal of Molecular Catalysis B-Enzymatic

    Google Scholar 

  123. Messager L, Burns JR, Kim J, Cecchin D, Hindley J, Pyne AL et al (2016) Biomimetic hybrid nanocontainers with selective permeability. Angew Chem Int Ed 55(37):11106–11109. https://doi.org/10.1002/anie.201604677

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the German Federal Ministry of Education and Research (Project Funding Reference Number 031B0221) for financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kathrin Castiglione.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Klermund, L., Castiglione, K. Polymersomes as nanoreactors for preparative biocatalytic applications: current challenges and future perspectives. Bioprocess Biosyst Eng 41, 1233–1246 (2018). https://doi.org/10.1007/s00449-018-1953-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00449-018-1953-9

Keywords

Navigation