Kendiliğinden Montajlı Peptidler ve Kullanım Alanları

Abstract

Moleküler kendiliğinden montaj, moleküllerin kovalent olmayan etkileşimler yoluyla biraraya gelerek supramoleküler yapılar oluşturduğu doğal bir mekanizmadır. Doğada mevcut olan nano ve mikro yapıdaki kendiliğinden montaj mekanizmalarının taklit edilmesiyle, istenilen özellikte çeşitli materyallerin tasarlanması mümkündür. Bu nanoyapılar, karbonhidrat, nükleik asitler ve peptidler gibi yapı taşlarının kendiliğinden montajıyla oluşmakla birlikte bunlar arasında kendiliğinden montajlı peptidler biyouyumluluk, biyobozunurluk ve kimyasal çeşitlilik yönünden en umut verici olanıdır. Peptitlerin kendi kendine montaj özelliklerinden yararlanılarak, nanotüpler, nano lifler, nano küreler, nano kapsüller ve hidrojeller gibi çok sayıda nanoyapı elde edilmiştir. Kendiliğinden montajlı peptid nanoyapılarının işlevi, uygun peptid bloklarının tasarımı ile ayarlanırken stabilite ve aktivitesi sıcaklık, pH, ışık ve elektriksel kuvvet gibi dış uyarıcılar kullanılarak değiştirilebilmektedir. Bugüne kadar peptidlerin kendiliğinden montaj mekanizması kullanılarak çok sayıda işlevsel materyal tasarlanmış ve bu materyaller birçok alanda uygulama imkanı bulmuştur. Bunlar arasında en çok öne çıkanlar, ilaç salınımı ve doku mühendisliği uygulamalarıdır. Bu derlemede, kendiliğinden montajlı peptid yapı blokları, kendiliğinden montaj mekanizması ve kendiliğinden montajlı peptid nanoyapıların uygulama alanları üzerinde durulmuştur.

Keywords

• Kendiliğinden montajlı peptidler
• ilaç salınımı
• enkapsülasyon
• doku mühendisliği
• antimikrobiyal uygulamalar

Self-Assembled Peptides and Their Applications

Abstract

Molecular self-assembly is a natural mechanism by which molecules come together through non-covalent interactions to form supramolecular structures. It is possible to design various materials with the desired properties by mimicking the self-assembling mechanisms in the nano and micro structures present in nature. Although these nanostructures are formed by self-assembly of building blocks such as carbohydrates, nucleic acids and peptides, self-assembled peptides are the most promising in terms of biocompatibility, biodegradability and chemical diversity. By utilizing the self-assembly properties of peptides, many nanostructures such as nanotubes, nanofibers, nanospheres, nanocapsules and hydrogels have been produced. The function of the self-assembled peptide nanostructures can be adjusted by the design of suitable peptide blocks, while the stability and activity can be altered using external stimulants such as temperature, pH, light and electrical force. To date, a large number of functional materials have been designed using the self-assembly mechanism for peptides and they have been applied in many areas. The most prominent of these are drug release and tissue engineering applications. In this review, self-assembled peptide building blocks, the self-assembly mechanism and the application areas of self-assembled peptide nanostructures have been discussed.

Keywords

• Self-assembled peptides
• drug release
• tissue engineering
• encapsulation
• antimicrobial applications

References

1. 1. Whitesides, G., J. Kriebel, and B. Mayers, Self-assembly and nanostructured materials. In Nanoscale Assembly. editör: Springer, Boston, MA., 2005. p. 217–238.
2. 2. Habibi, N., et al., Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery. Nano Today, 2016. 11(1): p. 41–60. https://doi.org/10.1016/j.nantod.2016.02.004.
3. 3. Ateş, H., ve E. Bahçeci, Nano Malzemeler için Üretim Yöntemleri. GU J Sci Part: C, 2015. 3(2): p.483-499.
4. 4. Mandal, D., A.N. Shirazi, and K. Parang, Self-Assembly of Peptides to Nanostructures. Org Biomol Chem., 2014. 12(22). doi: 10.1039/c4ob00447g. Epub 2014 Apr 23.
5. 5. Lowik, D., and J.C.M.Van Hest, Peptide based amphiphiles. Chem Soc Rev., 2004. 33(4): p. 234–245. DOI: 10.1039/b212638a.
6. 6. Antonietti, M., and S. Forster, Vesicles and liposomes: a self-assembly principle beyond lipids. Adv Mater Deerfield, 2003. 15(16): p. 1323–1333. DOI: 10.1002/adma.200300010.
7. 7. Liu, L., et al., The role of self-assembling polypeptides in building nanomaterials. Phys Chem., 2011. 13(39): p. 17435–17444. DOI: 10.1039/c1cp21338e.
8. 8. Gore, T, et al., Self-assembly of model collagen peptide amphiphiles. Langmuir, 2001. 17(17): p. 5352–5360. https://doi.org/10.1021/la010223i.

9. 9. Tu, R.S., and M. Tirrell, Bottom-up design of biomimetic assemblies. Adv Drug Deliv Rev., 2004. 56(11): p. 1537–1563. https://doi.org/10.1016/j.addr.2003.10.047.
10. 10. Caplan, M.R., et al., Lauffenburger DA. Control of self-assembling oligopeptide matrix formation through systematic variation of amino acid sequence. Biomaterials, 2002. 23(1): p. 219–227. https://doi.org/10.1016/S0142-9612(01)00099-0.
11. 11. Vauthey, S., et al., Molecular self-assembly of surfactant-like peptides to form nanotubes and nano-vesicles. Proc Natl Acad Sci USA, 2002. 99(8): p.5355–5360. https://doi.org/10.1073/pnas.072089599.
12. 12. Von Maltzahn, G., et al., Positively charged surfactant-like peptides self-assemble into nanostructures. Langmuir, 2003. 19(10): p. 4332–4337. https://doi.org/10.1021/la026526+.
13. 13. Hosseinkhani, H., P.D. Hong, and D.S. Yu, Self-assembled proteins and peptides for regenerative medicine. Chem Rev, 2013. 113(7): p. 4837–4861. https://doi.org/10.1021/cr300131h.
14. 14. Cui, H., M.J. Webber, and S.I. Stupp, Self-assembly of peptide amphiphiles: from molecules to nanostructures to biomaterials. Biopolymers, 2010. 94(1): p. 1–18. https://doi.org/10.1002/bip.21328.
15. 15. Dehsorkhi, A., V. Castelletto, and I.W. Hamley, Self-assembling amphiphilic peptides. J Pept Sci., 2014. 20: p. 453–467. https://doi.org/10.1002/psc.2633.
16. 16. Edwards-Gayle, C.J.C., and I.W. Hamley, Self-assembly of bioactive peptides, peptide conjugates, and peptide mimetic materials. Org Biomol Chem., 2017. 15: p. 5867. https://doi.org/10.1039/c7ob01092c.
17. 17. Song, Z., et al., Self-assembly of peptide amphiphiles for drug delivery: the role of peptide primary and secondary structures. Biomater Sci., 2017. 5(12): p. 2369-2380. DOI:10.1039/c7bm00730b.
18. 18. Zhang, S., et al., Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proc Natl Acad Sci USA, 1993. 90(8): p. 3334–3338. https://doi.org/10.1073/pnas.90.8.3334.
19. 19. Zhang, S., et al., Unusually stable beta-sheet formation in an ionic self-complementary oligopeptide. Biopolymers, 1994. 34(5): p. 663–672. https://doi.org/10.1002/bip.360340508.
20. 20. Zhang S, et al., Self-complementary oligopeptide matrices support mammalian cell attachment. Biomaterials, 1995. 16(18):p. 1385–1393. https://doi.org/10.1016/0142-9612(95)96874-Y.
21. 21. Kim, S, et al., Beta-sheet-forming, self-assembled peptide nanomaterials towards optical, energy, and healthcare applications. Small, 2015. 11(30): p. 3623–3640. https://doi.org/10.1002/smll.201500169.
22. 22. Zhao, X.B., et al., Molecular self-assembly and applications of designer peptide amphiphiles. Chem Soc Rev., 2010. 39(9): p. 3480–3498. DOI:10.1039/b915923c.
23. 23. Zhang, S.G., Emerging biological materials through molecular self-assembly. Biotechnol Adv., 2002. 20(5–6): p. 321–339. https://doi.org/10.1016/S0734-9750(02)00026-5.
24. 24. Yokoi H., T. Kinoshita, and S.G. Zhang, Dynamic reassembly of peptide RADA16 nanofiber scaffold. Proc Natl Acad Sci USA, 2005. 102(24): p. 8414–8419. DOI:10.1073/pnas.0407843102.
25. 25. Yang, Y., et al., Designer self-assembling peptide nanomaterials. Nano Today, 2009. 4(2): p. 193–210. https://doi.org/10.1016/j.nantod.2009.02.009.
26. 26. Chen, P., Self-assembly of ionic-complementary peptides: a physicochemical viewpoint, Colloids and Surfaces A: Physicochem. Eng. Aspects 2005; 261: 3–24. https://doi.org/10.1016/j.colsurfa.2004.12.048.
27. 27. Davis, M.E., et al., Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells. Circulation, 2005. 111(4): p. 442–450. doi: 10.1161/01.CIR.0000153847.47301.80.
28. 28. Wen, Y., et al., Coassembly of amphiphilic peptide EAK16-II with histidinylated analogues and implications for functionalization of beta-sheet fibrils in vivo. Biomaterials, 2014. 35(19): p. 5196–5205. https://doi.org/10.1016/j.biomaterials.2014.03.009
29. 29. He, B., X. Yuanb, and D. Jiang, Molecular self-assembly guides the fabrication of peptide nanofiber scaffolds for nerve repair. RSC Adv., 2014. p. 45. https://doi.org/10.1039/c4ra01826e.
30. 30. Ghadiri, M.R., et al.,Self-assembling organic nanotubes based on a cyclic peptide architecture. Nature 1993. 366(6453): p. 324–327. DOI: 10.1038/366324a0.
31. 31. Hartgerink, J.D., et al., Self-assembling peptide nanotubes. J Am Chem Soc., 1996. 118(1): p.43–50. https://doi.org/10.1021/ja953070s.
32. 32. Ishihara, Y. and S. Kimura, Nanofiber formation of amphiphilic cyclic tri-𝛽-peptide. J Pept Sci., 2010. 16(2): p. 110–114. DOI: 10.1002/psc.1206.
33. 33. Chapman, R., et al., Design and properties of functional nanotubes from the selfassembly of cyclic peptide templates. Chem Soc Rev., 2012. 41(18): p. 6023–6041. DOI: 10.1039/c2cs35172b.
34. 34. De Santis, P., E. Forni, R. Rizzo, Conformational analysis of DNA-basic polypeptide complexes: possible models of nucleo protamines and nucleo histones. Biopolymers, 1974. 13(2): p. 313–326. DOI: 10.1002/bip.1974.360130207.
35. 35. Shaikh, H., et al., Hydrogel and Organogel Formation by Hierarchical Self-Assembly of Cyclic Peptides Nanotubes. Chem Eur J., 2018. 24: 19066–19074. https://doi.org/10.1002/chem.201804576.
36. 36. Lim, Y–b., E. Lee, and M. Lee, Controlled Bioactive Nanostructures from Self-Assembly of Peptide Building Blocks. Angew Chem Int Ed., 2007. 46: p. 9011-9014. https://doi.org/10.1002/anie.200702732.
37. 37. Mandal, D., et al., Self-assembled surfactant cyclic peptide nanostructures as stabilizing agents. Soft Matter, 2013. 9: p. 9465-9475. DOI: 10.1039/C3SM50764E.
38. 38. Adler-Abramovich, L. and E. Gazit, The physical properties of supramolecular peptide assemblies: from building block association to technological applications. Chem Soc Rev., 2014. 43: p. 6881–93. DOI: 10.1039/c4cs00164h.
39. 39. Fleming, S. and RV. Ulijn, Design of nanostructures based on aromatic peptide amphiphiles. Chem Soc Rev., 2014. 43: p. 8150–77. DOI:10.1039/c4cs00247d.
40. 40. Tang, C., R.V. Ulijn, and A. Saiani, Effect of glycine substitution on Fmoc–diphenylalanine self-assembly and gelation properties. Langmuir, 2011. 27: p. 14438–49. DOI: 10.1021/la202113j.
41. 41. Kuang, Y., et al., The first supramolecular peptidic hydrogelator containing taurine. Chem Commun., 2014. 50: p.2772–4. DOI: 10.1039/c3cc48832b.
42. 42. Ou, C., et al., Phenothiazine as an aromatic capping group to construct a short peptide-based ‘super gelator’. Chem Commun., 2013. 49: p. 1853–5. DOI: 10.1039/c3cc38409h.
43. 43. Garifullin, R. and M.O. Guler, Supramolecular chirality in self-assembled peptide amphiphile nanostructures. Chem Commun, 2015. 51: p. 12470–3. DOI: 10.1039/c5cc04982b.
44. 44. Tena‐Solsona, M., J.F. Miravet, and B. Escuder, Tetrapeptidic molecular hydrogels: self‐assembly and Coaggregation with amyloid fragment Aβ1‐40. Chem Eur J., 2014. 20: p. 1023–31. DOI: 10.1002/chem.201302651.
45. 45. Matsuzawa, Y. and N. Tamaoki, Photoisomerization of azobenzene units controls the reversible dispersion and reorganization of fibrous self-assembled systems. J Phys Chem B., 2010. 114: p. 1586–90. DOI: 10.1021/jp909460a.
46. 46. Zeng, G., et al., Transition of chemically modified diphenylalanine peptide assemblies revealed by atomic force microscopy. RSC Adv 2014. 4: p. 7516–20. DOI: 10.1039/c3ra46718j.
47. 47. Qin, S.Y., et al., Adjustable nanofibers self-assembled from an irregular conformational peptide amphiphile. Polym Chem, 2015. 6: p. 519–24. DOI: 10.1039/C4PY01237B.
48. 48. Martin, A.D., et al., A capped dipeptide which simultaneously exhibits gelation and crystallization behavior. Langmuir, 2016. 32: p. 2245–50. DOI: 10.1021/acs.langmuir.5b03963.
49. 49. Adler‐Abramovich, L. and E. Gazit, Controlled patterning of peptide nanotubes and nanospheres using inkjet printing technology. J Pept Sci., 2008. 14: p. 217–23. DOI: 10.1002/psc.963.
50. 50. Kopecek, J., Smart and genetically engineered biomaterials and drug delivery systems. Eur J Pharm Sci., 2003. 20(1): p. 1–16. https://doi.org/10.1016/S0928-0987(03)00164-7.
51. 51. Rajagopal, K. and J.P. Schneider, Self-assembling peptides and proteins for nanotechnological applications. Curr Opin Struct Biol., 2004. 14(4): p. 480–486. https://doi.org/10.1016/j.sbi.2004.06.006.
52. 52. Santana, H., et all., How does growth hormone releasing hexapeptide self-assemble in nanotubes? Soft Matter, 2014. 10(46): p. 9260–9269. DOI: 10.1039/C4SM01693A.
53. 53. Su, C.W., et al., Multifunctional nanocar¬riers for simultaneous encapsulation of hydrophobic and hydrophilic drugs in cancer treatment. Nanomedicine, 2014. 9(10): p. 1499–1515. DOI: 10.2217/nnm.14.97.
54. 54. Webber, M. J., et al., Controlled release of dexamethasone from peptide nanofiber gels to modulate inflammatory response. Biomaterials, 2012. 33(28): p. 6823–6832. DOI: 10.1016/j.biomaterials.2012.06.003.
55. 55. Yishay-Safranchik, E., M. Golan, and A. David, Controlled release of doxorubicin and Smac-derived pro-apoptotic peptide from self-assembled KLD-based peptide hydrogels. Polym Advan Technol, 2014. 25(5): p. 539–544. https://doi.org/10.1002/pat.3300.
56. 56. Yu, Z., et al., Self-assembling peptide nanofibrous hydrogel as a versatile drug delivery platform. Curr Pharm Des, 2015. 21(29): p. 4342–4354. DOI: 10.2174/1381612821666150901104821.
57. 57. Fan, T., et al., Peptide Self-Assembled Nanostructures for Drug Delivery Applications. Hindawi J Nanomater, 2017. p. 16. https://doi.org/10.1155/2017/4562474.
58. 58. Zhua, F., et al., Self-assembled polymeric micelles based on THP and THF linkage for pH-responsive drug delivery. Polymer, 2014. 55(13): p. 2977-2985. https://doi.org/10.1016/j.polymer.2014.05.010.
59. 59. Zou, L.L., et al., Cell-penetrating peptide-mediated therapeutic molecule delivery into the central nervous system. Curr Neuropharmacol, 2013. 11(2): p.197-208. DOI: 10.2174/1570159X11311020006.
60. 60. Zhang, P., et al., Self-assembled tat nanofibers as effective drug carrier and transporter. Acs Nano, 2013. 7(7): p. 5965–5977. DOI: 10.1021/nn401667z.
61. 61. Silva, G.A., et al., Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science, 2004. 303(5662): p. 1352–1355. DOI: 10.1126/science.1093783.
62. 62. Wan, A.C.A. and J.Y.Ying, Nanomaterials for in situ cell delivery and tissue regeneration. Adv Drug Deliv Rev, 2010. 62(7–8): p. 731–740. DOI: 10.1126/science.1093783.
63. 63. Kisiday, J., et al., Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair. Proc Natl Acad Sci USA, 2002.99(15): p. 9996–10001. DOI: 10.1073/pnas.142309999.
64. 64. Hosseinkhani, H., et al., Osteogenic differentiation of mesenchymal stem cells in self assembled-peptide amphiphile nanofibers. Biomaterials, 2006. 27: p. 4079. https://doi.org/10.1016/j.biomaterials.2006.03.030.
65. 65. Keung, A.J., S. Kumar, and D.V. Schaffer, Presentation Counts: Microenvironmental Regulation of Stem Cells by Biophysical and Material Cues. Annu Rev Cell Dev Biol., 2010. 26: p. 533–556. DOI: 10.1146/annurev-cellbio-100109-104042.
66. 66. Hartgerink, J.D., E. Beniash, and S.I. Stupp, Self-assembly and mineralization of peptide amphiphile nanofibers. Science, 2001. 294: p. 1684. DOI: 10.1126/science.1063187.
67. 67. Beniash, E., et al., Self-assembling peptide amphiphile nanofiber matrices for cell entrapment. Acta Biomater, 2005. 1: p. 387. DOI: 10.1016/j.actbio.2005.04.002.
68. 68. Sargeant, T. D., Hybrid bone implants: Self-assembly of peptide amphiphile nanofibers within porous titanium. Biomaterials, 2008. 29: p.161. https://doi.org/10.1016/j.biomaterials.2007.09.012.
69. 69. Van Kan, E.J.M., et al., Membrane activity of the peptide antibiotic clavanin and the importance of its glycine residues. Biochemistry, 2001. 40(21): p. 6398–6405. DOI: 10.1021/bi0028136.
70. 70. Galanth, C., et al., Mechanism of antibacterial action of dermaseptin B2: interplay between helix-hinge-helix structure and membrane curvature strain. Biochemistry, 2009. 48(2): p. 313-27. doi: 10.1021/bi802025a.
71. 71. Chen, C., et al., Antibacterial activities of short designer peptides: a link between propensity for nanostructuring and capacity for membrane destabilization. Biomacromolecules, 2010. 11(2): p. 402–411. https://doi.org/10.1021/bm901130u.
72. 72. Veiga, A.S., et al., Arginine-rich self-assembling peptides as potent antibacterial gels. Biomaterials, 2012. 33(35): p. 8907–8916. DOI: 10.1016/j.biomaterials.2012.08.046.
73. 73. Häffner, S.M. and M. Malmsten, Influence of self-assembly on the performance of antimicrobial peptides. ‎Curr Opin Colloid Interface Sci., 2018. 38: p. 56-79. https://doi.org/10.1016/j.cocis.2018.09.002.
74. 74. Schnaider, L., et al., Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity. Nat Commun., 2017. 8: p. 1365. DOI: 10.1038/s41467-017-01447-x.
75. 75. Rodríguez-Vázquez, N., et al., Membrane-targeted self-assembling cyclic peptide nanotubes. Curr Top Med Chem., 2014. 14(23): p. 2647-61. DOI: 10.2174/1568026614666141215143431.
76. 76. Salick, D.A., et al., Inherent antibacterial peptide-based b-hairpin hydrogel. J Am Chem Soc., 2007. 129: p. 14793–14799. DOI: 10.1021/ja076300z.
77. 77. Salick, D.A., D.J. Pochan, and J.P.Schneider, Design of an injectable b-hairpin peptide hydrogel that kills methicillin resistant Staphylococcus aureus. Adv Mater., 2009. 21: p. 4120–4123. DOI: 10.1002/adma.200900189.
78. 78. Lombardi, L., et al., Enhancing the Potency of Antimicrobial Peptides through Molecular Engineering and Self-Assembly. Biomacromolecules, 2019. 20(3): p. 1362-1374. DOI: 10.1021/acs.biomac.8b01740.
79. 79. Liu, L., et al., Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent. Nat Nanotechnol., 2009. 4: p. 457–463. DOI: 10.1038/nnano.2009.153.
80. 80. Ahmed, E.M., Hydrogel: Preparation, characterization, and applications: A review. J Adv Res., 2015. 6: p. 105–121. https://doi.org/10.1016/j.jare.2013.07.006.
81. 81. Xing, R., et al., Self-Assembled Injectable Peptide Hydrogels Capable of Triggering Antitumor Immune Response. Biomacromolecules, 2017. 18(11): p. 3514-3523. DOI: 10.1021/acs.biomac.7b00787.
82. 82. Cheng, G., et al., Hydrogelation of self-assembling RGD-based peptides. Soft Matter, 2011. 7: p. 1326–1333. DOI: 10.1039/c0sm00408a.
83. 83. Laverty, G., et al., Ultrashort Cationic Naphthalene-Derived Self-Assembled Peptides as Antimicrobial Nanomaterials. Biomacromolecules, 2014. 15: p. 3429−3439. DOI: 10.1021/bm500981y.
84. 84. Albadr, A.A., S.M.Coulter, and S.L. Porter, Thakur RRS and Laverty G. Ultrashort Self-Assembling Peptide Hydrogel for the Treatment of Fungal Infections. Gels, 2018. 4(2): p. 48. DOI: 10.3390/gels4020048.
85. 85. Verma, G., V.K. Aswal, and P. Hassan, Ph-Responsive Self Assembly in an Aqueous Mixture of Surfactant and Hydrophobic Amino Acid Mimic. Soft Matter, 2009. 5: p. 2919−2927. DOI: 10.1039/b900891h.
86. 86. Tine, M.R., et al., Effect of Temperature on Self-Assembly of an Ionic Tetrapeptide. J Therm Anal Calorim., 2011. 103: p. 75−80. DOI: 10.1007/s10973-010-1060-x.
87. 87. Ozores, H.L., M. Amorín, and J.R.Granja, Self-Assembling Molecular Capsules Based on α,γ-Cyclic Peptides. J Am Chem Soc., 2017. 139(2): p. 776-784. DOI: 10.1021/jacs.6b10456.
88. 88. Fung, S.Y., et al., Concentration Effect on the Aggregation of a Self-Assembling Oligopeptide. Biophys J., 2003. 85(1): p. 537–548. https://doi.org/10.1016/S0006-3495(03)74498-1.
89. 89. Jin, W., X. Shi, and F. Caruso, High Activity Enzyme Microcrystal Multilayer Films. J Am Chem Soc., 2001. 123: p. 8121. https://doi.org/10.1021/ja015807l.
90. 90. Guler, M.O., R.C. Claussena, and S.I. Stupp, Encapsulation of pyrene within self-assembled peptideamphiphile nanofibers. J Mater Chem., 2005. 15(42). DOI: 10.1039/b509246a.
91. 91. Chang, R., L. Sun, and T.J. Webster, Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres. Int J Nanomedicine, 2015. 10: p. 3351–3365. doi: 10.2147/IJN.S78756.
92. 92. Kim, I., et al., A “light-up” 1D supramolecular nanoprobe for silver ions based on assembly of pyrene-labeled peptide amphiphiles: cell-imaging and antimicrobial activity. J Mat Chem., 2014. 2(38): p. 6478–6486. DOI: 10.1039/C4TB00892.