pubs.acs.org/Langmuir © 2010 American Chemical Society
Catechol-Grafted Poly(ethylene glycol) for PEGylation on Versatile Substrates Hyukjin Lee,† Kang Dae Lee,‡ Kyung Bo Pyo,‡ Sung Young Park,*,§ and Haeshin Lee*,† †
Department of Chemistry, Graduate School of Nanoscience & Nanotechonology, Molecular-level Interface Research Center, KAIST, ‡Department of Otolaryngology-Head and Neck Surgery, Kosin University College of Medicine, and §Department of Chemical and Biological Engineering, Chungju National University, Republic of Korea Received December 29, 2009. Revised Manuscript Received February 2, 2010 We report on catechol-grafted poly(ethylene) glycol (PEG-g-catechol) for the preparation of nonfouling surfaces on versatile substrates including adhesion-resistant PTFE. PEG-g-catechol was prepared by the step-growth polymerization of PEO to which dopamine, a mussel-derived adhesive molecule, was conjugated. The immersion of substrates into an aqueous solution of PEG-g-catechol resulted in robust PEGylation on versatile surfaces of noble metals, oxides, and synthetic polymers. Surface PEGylation was unambiguously confirmed by various surface analytical tools such as ellipsometry, goniometry, infrared spectroscopy, and X-ray photoelectron spectroscopy. Contrary to existing PEG derivatives that are difficult-to-modify synthetic polymer surfaces, PEG-g-catechol can be considered to be a new class of PEGs for the facile surface PEGylation of various types of surfaces.
Introduction The development of strategies to prepare nonfouling surfaces is essential for biomedical devices. The nonspecific adsorption of proteins and cells at solid-liquid interfaces often leads to adverse effects such as a foreign-body inflammatory response that causes device failure.1-5 This severe limitation of medical devices can be improved by biocompatible surface modifications. Examples include the incorporation of alkanethiols with end-functionalized oligo-ethylene glycol moieties and varieties of other antifouling polymers.6-8 Among these approaches, minimizing the nonspecific adsorption of biomolecules by the robust immobilization of poly(ethylene glycol) (PEG) on surfaces has been widely implemented. It is known that PEG molecules exhibit a stealth effect because of the large hydrodynamic volume caused by bound water molecules.9,10 To immobilize PEG molecules onto surfaces, specific interactions between interfacial modifiers and surfaces are required; possible interactions include thiolate on noble metals, phosphonic *To whom correspondence should be addressed. E-mail: parkchem@ cjnu.ac.kr,
[email protected]. (1) Ratner, B. D. J. Biomed. Mater. Res. 1993, 27, 283–288. (2) Wisniewski, N.; Reichert, M. Colloids Surf., B 2000, 18, 197–219. (3) Shen, M.; Horbett, T. A. J. Biomed. Mater. Res. 2001, 57, 336–345. (4) Thomsen, P.; Gretzer, C. Curr. Opin. Solid State Mater. Sci. 2001, 5, 163– 176. (5) Ostuni, E.; Chapman, R. G.; Liang, M. N.; Melueni, G.; Pier, G.; Ingber, D. E.; Whitesides, G. M. Langmuir 2001, 17, 6336–6343. (6) Nath, N.; Hyun, J.; Ma, H.; Chilkoti, A. Surf. Sci. 2004, 570, 98–110. (7) Mrksich, M.; Whitesides, G. M. Annu. Rev. Biophys. Biomol. Struct. 1996, 25, 55–78. (8) Brodbeck, W. G.; Shive, M. S.; Colton, E.; Nakayama, Y.; Matsuda, T.; Anderson, J. M. J. Biomed. Mater. Res. 2001, 55, 661–668. (9) Andrade, J. D.; Hlady, V. Adv. Polym. Sci. 1986, 79, 1–63. (10) Jeon, S. I.; Lee, J. H.; Andrade, J. D.; Degannes, P. G. J. Colloid Interface Sci. 1991, 142, 149–158. (11) Golander, C. G.; Herron, J. N.; Lim, K.; Claesson, P.; Stenius, P.; Andrade, J. D. In Poly(ethylene glycol) Chemistry; Harris, J. M, Ed.; Plenum Press: New York, 1992. (12) Popat, K. C.; Sharma, S.; Desai, T. A. J. Phys. Chem. B 2004, 108, 5185– 5188. (13) Ademovic, Z.; Holst, B.; Kahn, R. A.; Jorring, I.; Brevig, T.; Wei, J.; Hou, X.; Winter-Jensen, B.; Kingshott, P. J. Mater. Sci. 2006, 17, 203–211.
3790 DOI: 10.1021/la904909h
acid on titanium oxides, and organosilane and polyamines on various oxides.11-13 In contrast to these surface-specific interactions, an emerging surface-independent interfacial modifier was recently reported.14-17 Catechol, a side chain of an unusual amino acid of 3,4-dihydroxy-L-phenylalanine (DOPA) found extensively in mussel-adhesive proteins, played a role in a surface-independent anchor molecule.18,19 When catecholic molecules are oligoor multimerized, they can bind to versatile material surfaces including hydrophobic, fluorine-containing materials such as poly(tetrafluoroethylene) (PTFE).17 Although the mechanism is not fully understood, the oligo- or multimerization of catechols increases the interfacial binding force, which has proven to produce powerful surface-anchoring moieties, functionalizing any type of material surface.17,20,21 In this study, we developed a new synthesis strategy to incorporate multiple catechol moieties along a PEG backbone to utilize the adhesive benefit of the repeated occurrence of catechols. Catecholgrafted poly(ethylene glycol) (PEG-g-catechol) was synthesized using step-growth polymerization, which resulted in the introduction of multiple catechols along PEG chains in a grafted manner rather than end functionalization. Previous studies showed that end-functionalized PEG-catechols could be immobilized on limited types of substrates such as titanium oxide (TiO2), gold, and stainless steel.14,15 Inspired by the enhanced surface PEGylation by multiple binding residues, lysine, in PLL-g-PEG, it is expected that the multiple catechols in PEG-g-catechol can be a suitable (14) Dalsin, J. L.; Hu, B.; Lee, B. P.; Messersmith, P. B. J. Am. Chem. Soc. 2003, 125, 4253–4258. (15) Dalsin, J. L.; Lin, L.; Tosatti, S.; Voros, J.; Textor, M.; Messersmith, P. B. Langmuir 2005, 21, 640–646. (16) Statz, A. R.; Meagher, R. J.; Barron, A. E.; Messersmith, P. B. J. Am. Chem. Soc. 2005, 127, 7972–7973. (17) Lee, H.; Dellatore, S. M.; Miller, W. M.; Messersmith, P. B. Science 2007, 318, 426–430. (18) Waite, J. H.; Tanzer, M. L. Science 1981, 212, 1038–1040. (19) Lee, H.; Scherer, N. F.; Messersmith, P. B. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 12999–13003. (20) Waite, J. H. Comp. Biochem. Physiol., Part B 1990, 97, 19–29. (21) Kang, S.; Rho, J.; Choi, I. S.; Messersmith, P. B.; Lee, H. J. Am. Chem. Soc. 2009, 131, 13224–13225.
Published on Web 02/11/2010
Langmuir 2010, 26(6), 3790–3793
Lee et al.
Letter
polymeric architecture for versatile-surface PEGylation rather than end-functionalized PEG-catechols.22-24 Various surface techniques such as goniometry, ellipsometry, infrared spectroscopy (PM-IRRAS), and X-ray photoelectron spectroscopy (XPS) clearly demonstrated that PEG-g-catechol was able to modify versatile surfaces including noble metals, metal oxides, and synthetic polymers.
Scheme 1. Illustration of the Synthesis of Catechol-Grafted Poly(ethylene glycol)
Experimental Section Materials. Poly(ethylene glycol) (Mn = 500), methoxy-poly(ethylene glycol) (mPEG, Mn 2000) epichlorohydrin, ethanol, dioxane, 30 -hydroxytyramine hydrochloride, N,N,-diisopropylethylamine (DIPEA), and 1-methyl-4-pyrrolidone (NMP) were purchased from Aldrich (Milwaukee, WI). N,N0 -Dimethylethylenediamine were purchased from TCI (Tokyo, Japan). All solvents were dried by standard procedures and distilled before use. Synthesis of Catechol-Grafted Poly(ethylene glycol) Polymer. OH side group-bearing PEG polymer (1 g, 1.16
10-4 mol) was dissolved in anhydrous dichloromethane (50 mL) and activated by a 2 molar excess of n-nitrophenyl-chloroformate (NPC) with respect to pending OH groups for 3 h. NPC-activated PEG polymer was collected by precipitation in cold diethyl ether and then dried under vacuum. The resulting product (500 mg) was dissolved in 1-methyl-4-pyrrolidone (NMP) (50 mL), and a 1.5 molar excess of 3-hydroxytyramine (dopamine) with respect to NPC was added to the solution with an equal molar amount of N,N,-diisopropylethylamine (DIPEA). The reaction was kept at 60 °C for 12 h. The resulting PEG-g-catechol polymers were dialyzed (MWCO = 3500 Da) for 2 days under acidic pH conditions (pH 3 to 4) to prevent the oxidative polymerization of catechols, and then the sample was lyophilized. The content of catechol conjugation was monitored at 280 nm using a UV-vis spectrophotometer (HP8453, Agilent). Serially diluted solutions of dopamine (0.125-0.015 mg/mL) were used to generate a calibration curve to determine the degree of dopamine conjugation.
Surface Modification Using PEG-g-catechol Polymer. Solid substrates were cleaned in either acetone or ethanol for 5 min with sonication. Surface modification using PEG-g-catechol was performed by immersing substrates in a buffer solution (10 mM Tris, pH 8.5) with 10 mg/mL of PEG-g-catechol at room temperature. After 12 h of incubation, the coated substrates were rinsed extensively with deionized water and dried under a stream of argon for further experiments. Characterization. Static water contact angles were measured using a Phoenix 300 goniometer (Surface Electro Optics Co., Ltd., Korea). Spectroscopic ellipsometry (Gaertner Scientific Co., IL) was used to determine the film thickness with a He-Ne laser (632.8 nm) at a 70° angle of incidence. XPS spectra were obtained to measure the surface atomic composition using an Omicrometer ESCALAB (Omicrometer, Taunusstein, Germany) with a monochromated Al KR (1486.8 eV) 300 W X-ray source under ultrahigh vacuum (
