Polimerik Veziküller ve Biyolojik Uygulamaları

Öz

Bilimin gelişmesindeki temel yaklaşım olan doğayı taklit etme çabasının günümüzdeki en son örneklerinden birisi polimerik veziküler sistemlerdir. Hücresel bölümlendirmenin yapıtaşı olan fosfolipitlerin kendiliğinden oluşum süreci ile veziküler yapıları oluşturması sürecinin, sentetik amfifilik kopolimerler üzerinde uygulanması ile üretilen polimerik veziküllerin biyolojik uygulamaları, özellikle eczacılık ve tıp alanında büyük ilgi görmüştür. Polimerik veziküller, kopolimerin hidrofobik bloğunun su ile temasını en aza indirgemek için yan yana gelerek çifte tabakalı bir membran oluşturması ve bu membranın sulu ortamı çevrelemesiyle meydana gelen mikroskopik/nanoskopik partiküllerdir. Yapılarındaki sulu lümen içerisinde hidrofilik molekülleri barındırabilen bu sistemler aynı zamanda hidrofobik molekülleri kopolimerik vezikül membranı içerisinde taşıyabilmektedirler. Dolayısıyla, yapısında her türlü molekülü taşıyabilme kapasitesi olan ve üretilen çeşitli kopolimerler ile kendisine farklı uygulama alanları bulmuş polimerik veziküller, araştırmacılar tarafından çoğunlukla ilaç taşıyıcı sistemler, medikal görüntüleme ajanları, nanoreaktörler ve son yıllarda da kendiliğinden çalışan nanomotorlar olarak kullanılmaktadır. Bu derleme ile, polimerik veziküller üzerinde çalışma yapacak bilim insanlarına/araştırmacılara genel bir perspektifin sunulması ve güncel bilgilerin bir arada verilmesi amaçlanmıştır.

Anahtar Kelimeler

• polimerik vezikül, polimerzom, ilaç taşıyıcı sistem, yapay hücre

Polymeric Vesicles and Biological Applications

Abstract

One of the most recent example of the effort to imitate nature which is the basic approach for the development of science, is the polymeric vesicular systems. The biological applications of the polymeric vesicles produced by the application of self-assembly process of vesicle forming phospholipids which are the building blocks of cellular compartmentalization, on synthetic amphiphilic copolymers, have attracted considerable interest, especially in the field of pharmaceutics and medicine. Polymeric vesicles are microscopic / nanoscopic particles which are formed by the confinemet of an aqueous environment by the copolymeric bilayer membrane which is shaped by the aim of minimizing the contact angle between the hydrophobic block of the copolymer and water. These systems, which can contain hydrophilic molecules in their aqueous lumen, can also carry hydrophobic molecules in the copolymeric vesicle membrane. Therefore, polymeric vesicles, which have the capacity to carry all kinds of molecules in the structure and can be produced from various copolymers, have been utilized in different application areas such as drug delivery systems, medical imaging agents, nanoreactors and self-propelling nanomotors in recent years. With this review, it is aimed to present a general perspective to scientists / researchers who will work onpolymeric vesicles and along with outlining the current information in the field.

Keywords

• polymeric vesicle, polymersome, drug delivery system, protocell

References

1. 1. Massignani M, Lomas H, Battaglia G. Polymersomes: A Synthetic Biological Approach to Encapsulation and Delivery. In: Carusco, ed. F.Modern Techniques for Nano- and Microreactors/-reactions. Heidelberg: Springer, 2010: 115-54.
2. 2. Alberts B, Johnson A, Lewıs J, Walter P, Raff M, Roberts K. Molecular Biology of the Cell 4th ed. New York: Routledge, 2002.
3. 3. Ahmed F, Pakunlu R, Brannan A, Bates F, Minko T, Discher DE. Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug. Journal of Controlled Release, 2006; 116(2): 150-8.
4. 4. Lomas H, Du J, Canton I, Madsen J, Warren N, Armes SP, et al. Efficient encapsulation of plasmid DNA in pH-sensitive PMPC-PDPA polymersomes: Study of the effect of PDPA block length on copolymer-DNA binding affinity. Macromolecular Bioscience, 2010; 10(5): 513-30.
5. 5. Rameez S, Alosta H, Palmer AF. Biocompatible and biodegradable polymersome encapsulated hemoglobin: A potential oxygen carrier. Bioconjugate Chemistry, 2008; 19(5): 1025-32.
6. 6. Gaitzsch J, Appelhans D, Wang L, Battaglia G, Voit B. Synthetic bio-nanoreactor: Mechanical and chemical control of polymersome membrane permeability. Angewandte Chemie - International Edition, 2012; 51(18): 4448-51.
7. 7. Huang WC, Chen YC, Hsu YH, Hsieh WY, Chıu HC. Development of a diagnostic polymersome system for potential imaging delivery. Colloids and Surfaces B: Biointerfaces, 2015; 128: 67-76.
8. 8. Discher BM, Won YY, Ege DS, Lee JCM, Bates FS, Discher DE, et al. Polymersomes: Tough vesicles made from diblock copolymers. Science, 1999; 284: 1143-6.

9. 9. Bozkır A, Kocyiğit S. An investigation of physical and chemical stabilities of liposomes. Journal of Faculty of Pharmacy of Ankara University, 1995; 24(1): 42-52.
10. 10. Ayen WY, Garkhal K, Kumar N. Doxorubicinloaded (PEG)-PLA nanopolymersomes: effect of solvents and process parameters on formulation development and in vitro study. Molecular Pharmaceutics, 2011; 8(2): 466-78.
11. 11. Shen H, Eisenberg A. Morphological phase diagram for a ternary system of block copolymer PS310-b-PAA52/Dioxane/H2O. The Journal of Physical Chemistry B, 1999; 103(44): 9473-87.
12. 12. Axthelm F, Casse O, Koppenol WH, Nauser T, Meier W, Palivan CG. Antioxidant nanoreactor based on superoxide dismutase encapsulated in superoxide-permeable vesicles. The Jounal of Physical Chemistry B, 2008; 112(28): 8211-7.
13. 13. Lorenceau E, Utada AS, Link DR, Cristobal G, Joanicot M, Weitz DA. Generation of polymerosomes from double-emulsions. Langmuir, 2005; 21(20): 9183-6.
14. 14. Ho CS, Kim JW, Weitz DA. Microfluidic fabrication of monodisperse biocompatible and biodegradable polymersomes with controlled permeability. Journal of the American Chemical Society, 2008; 130(29): 9543-9.
15. 15. Habault D, Dery A, Leng J, Lecommandoux S, Le Meins JF, Sandre O. Droplet microfluidics to prepare magnetic polymer vesicles and to confine the heat in magnetic hyperthermia. IEEE Transactions on Magnetics, 2013; 49(1): 182-90.
16. 16. Thiele J, Steinhauser D, Pfohl T, Förster S. Preparation of monodisperse block copolymer vesicles via flow focusing in microfluidics. Langmuir, 2010; 26(9): 6860-3.
17. 17. Romanowsky MB, Abate AR, Rotem A, Holtze C, Weitz DA. High throughput production of single core double emulsions in a parallelized microfluidic device. Lab Chip, 2012; 12(4): 802- 7.
18. 18. Du J, Tang Y, Lewis AL, Armes SP. pH-sensitive vesicles based on a biocompatible zwitterionic diblock copolymer. Journal of the American Chemical Society, 2005; 127(51): 17982-3.
19. 19. Kishimura A, Koide A, Osada K, Yamasaki Y, Kataoka K. Encapsulation of myoglobin in PEGylated polyion complex vesicles made from a pair of oppositely charged block ionomers: A Physiologically available oxygen carrier. Angewandte Chemie International Edition, 2007; 46(32): 6085-8.
20. 20. Wan WM, Hong CY, Pan CY. One-pot synthesis of nanomaterials via RAFT polymerization induced self-assembly and morphology transition. Chem, Commun; 2009; (39): 5883-5.
21. 21. Battaglia G, Ryan AJ. Pathways of polymeric vesicle formation. Journal of Physical Chemistry B, 2006; 110(21): 10272-9.
22. 22. Photos PJ, Bacakova L, Discher B, Bates FS, Discher DE. Polymer vesicles in vivo: Correlations with PEG molecular weight. Journal of Controlled Release, 2003; 90(3): 323-34.
23. 23. Angelova MI, Dimitrov DS. Liposome electroformation. Faraday Discussions of the Chemical Society, 1986; 81(0): 303-11
24. 24. Lee James CM, Bermudez H, Discher BM, Sheehan MA, Won YY, Bates FS, et al. Preparation, stability, and in vitro performance of vesicles made with diblock copolymers. Biotechnology and Bioengineering, 2001; 73(2): 135-45.
25. 25. O’Neil CP, Suzuki T, Demurtas D, Finka A, Hubbell JA. A novel method for the encapsulation of biomolecules into polymersomes via direct hydration. Langmuir, 2009; 25(16): 9025-9.
26. 26. Ahmed F, Discher DE. Self-porating polymersomes of PEG-PLA and PEG-PCL: Hydrolysis-triggered controlled release vesicles. Journal of Controlled Release, 2004; 96(1): 37-53.
27. 27. Geng Y, Discher DE. Visualization of degradable worm micelle breakdown in relation to drug release. Polymer, 2006; 47(7): 2519-25.
28. 28. Balasubramanian V, Herranz-Blanco B, Almeida PV, Hirvonen J, Santos HA. Multifaceted polymersome platforms: Spanning from self-assembly to drug delivery and protocells. Progress in Polymer Science, 2016; 60: 51-85.
29. 29. Torchilin VP, Lukyanov AN. Peptide and protein drug delivery to and into tumors: Challenges and solutions. Drug Discovery Today, 2003; 8(6): 259- 66.
30. 30. Liu G, Ma S, Li S, Cheng R, Meng F, Liu H, et al. The highly efficient delivery of exogenous proteins into cells mediated by biodegradable chimaeric polymersomes. Biomaterials, 2010; 31(29): 7575- 85.
31. 31. Barnier Quer C, Robson Marsden H, Romeijn S, Zope H, Kros A, Jiskoot W. Polymersomes enhance the immunogenicity of influenza subunit vaccine. Polymer Chemistry, 2011; 2(7): 1482-5.
32. 32. Scott Ea, Stano A, Gillard M, Maio-Liu AC, Swartz MA, Hubbell JA. Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes. Biomaterials, 2012; 33(26): 6211-9.
33. 33. Pang Z, Gao H, Yu Y, Guo L, Chen J, Pan S, Ren J, Wen Z, Jıang X. Enhanced intracellular delivery and chemotherapy for glioma rats by transferrinconjugated biodegradable polymersomes loaded with doxorubicin. Bioconjugate Chemistry, 2011; 22(6): 1171-80.
34. 34. Huang J, Bonduelle C, Thévenot J, Lecommandoux S, Heise A. Biologically active polymersomes from amphiphilic glycopeptides. Journal of the American Chemical Society, 2012; 134(1): 119-22.
35. 35. Lee JS, Groothuıs T, Cusan C, Mink D, Feijen J. Lysosomally cleavable peptide-containing polymersomes modified with anti-EGFR antibody for systemic cancer chemotherapy. Biomaterials, 2011; 32(34): 9144-53.
36. 36. Pangburn TO, Bates FS, Kokkoli E. 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. Soft Matter, 2012; 8(16): 4449-61.
37. 37. Egli S, Nussbaumer MG, Balasubramanian V, Chami M, Bruns N, Palivan C, et al. Biocompatible functionalization of polymersome surfaces: A new approach to surface immobilization and cell targeting using polymersomes. Journal of the American Chemical Society, 2011; 133(12): 4476-83.
38. 38. Robbins GP, Saunders RL, Haun JB, Rawson J, Therien MJ, Hammer DA. Tunable leukopolymersomes that adhere specifically to inflammatory markers. Langmuir, 2010; 26(17): 14089-96.
39. 39. Ghoroghchian PP, Frail PR, Li G, Zupancich JA, Bates FS, Hammer DA, et al. Controlling bulk optical properties of emissive polymersomes through intramembranous polymer-fluorophore interactions. Chemistry of materials : a publication of the American Chemical Society, 2007; 19(6): 1309-18.
40. 40. Massignani M, Canton I, Sun T, Hearnden V, Macneil S, Blanazs A, Armes SP, Lewis A, Battaglıa G. Enhanced fluorescence imaging of live cells by effective cytosolic delivery of probes. Plos One, 2010; 5(5): e10459.
41. 41. Duncan TV, Ghoroghchian PP, Rubtsov IV, Hammer DA, Therien MJ. Ultrafast excited-state dynamics of nanoscale near-infrared emissive polymersomes. Journal of the American Chemical Society, 2008; 130(30): 9773-84.
42. 42. Cheng Z, Tsourkas A. Paramagnetic porous polymersomes. Langmuir, 2008; 24(15): 8169-73.
43. 43. Mueller W, Koynov K, Fischer K, Hartmann S, Pierrat S, Basché T, et al. Hydrophobic shell loading of PBb-PEO vesicles. Macromolecules, 2009; 42(1): 357- 61.
44. 44. P Stano. Synthetic biology of minimal living cells: primitive cell models and semi-synthetic cells. Systems and Synthetic Biology, 2010; 4(3): 149-56.
45. 45. Dzieciol AJ, Mann S. Designs for life: Protocell models in the laboratory. Chemical Society Reviews, 2012; 41(1): 79-85.
46. 46. Szostak JW, Bartel DP, Luisi PL. Synthesizing life. Nature, 2001; 409(6818): 387-90.
47. 47. Hanczyc MM, Szostak JW. Replicating vesicles as models of primitive cell growth and division. Current Opinion in Chemical Biology, 2004; 8(6): 660-4.
48. 48. Palivan CG, Fischer-Onaca O, Delcea M, Itel F, Meier W. Protein-polymer nanoreactors for medical applications. Chemical Society Reviews, 2012; 41(7): 2800-23.
49. 49. Kumar M, Grzelakowski M, Zilles J, Clark M, Meier W. Highly permeable polymeric membranes based on the incorporation of the functional water channel protein Aquaporin Z. Proceedings of the National Academy of Sciences, 2007; 104(52): 20719-24.
50. 50. Messager L, Burns JR, Kim J, Cecchin D, Hindley J, Pyne AL, et al. Biomimetic hybrid nanocontainers with selective permeability. Angew Chem Int Ed Engl, 2016; 55(37): 11106-9.
51. 51. Hammer DA, Kamat NP. Towards an artificial cell. FEBS Letters, 2012; 586(18): 2882-90.
52. 52. Martino C, Kim SH, Horsfall L, Abbaspourrad A, Rosser SJ, Cooper J, et al. Protein expression, aggregation, and triggered release from polymersomes as artificial cell-like structures. Angewandte Chemie - International Edition, 2012; 51(26): 6416-20.
53. 53. Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell, 2003; 112(4): 453-65.
54. 54. Van Oudenaarden A, Theriot JA. Cooperative symmetry-breaking by actin polymerization in a model for cell motility. Nat Cell Biol, 1999; 1(8): 493-9.
55. 55. Stachowiak JC, Richmond DL, Li TH, BrochardWyart F, Fletcher DA. Inkjet formation of unilamellar lipid vesicles for cell-like encapsulation. Lab on a chip, 2009; 9(14): 2003- 9.
56. 56. Lemière J, Carvalho K, Sykes C. Cell-sized liposomes that mimic cell motility and the cell cortex. In: Jennifer, R. Wallace, eds. Methods in Cell Biology. Oxford. Academic Press. 2015: 271- 85.
57. 57. Kamat NP, Katz JS, Hammer DA. Engineering polymersome protocells. The Journal of Physical Chemistry Letters, 2011; 2(13): 1612-23.
58. 58. Joseph A, Contini C, Cecchin D, Nyberg S, RuizPerez L, Gaitzch J, et al. Chemotactic synthetic vesicles: Design and applications in bloodbrain barrier crossing. Science Advances, 2017; 3(8):e1700362.