Communication pubs.acs.org/cm
Reversible Redox-Responsive Assembly/Disassembly of Nanoparticles Mediated by Metal Complex Formation Markus B. Bannwarth,*,†,‡ Thomas Weidner,† Evelyn Eidmann,† Katharina Landfester,† and Daniel Crespy*,† †
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128 Mainz, Germany
‡
S Supporting Information *
S
mechanism triggered by a redox stimulus (Figure 1). Magnetite nanoparticles with sizes of 10.2 ± 2.0 nm were employed as
ince Feynmans vision of nanobots performing tasks at the micro- and nanoscale,1 it is the dream of many chemists to develop complex materials that adapt their properties as a function of their environments and/or intended use.2 A control over the assembly of superstructures3 or heterogeneous conjuncts4 is a potential platform for materials with such behavior. One promising approach is to learn from biology to design synthetic systems with a high level of complexity.5 Bacteria are fascinating organisms that are counted among the first forms of life on Earth. One striking characteristic of bacteria is the variety of shapes they can adaptfrom spheroids to rods, spirals, and filaments. Modeled through evolution, the specific shape of a bacterium is largely influenced by their motility, resistance to desiccation and osmotic shock, aptitude to build biofilms, and ability to avoid predation.6 The morphology of a single species of bacteria is also not static, and there is evidence that shape change such as filamentation in stressful environments is a key part of the survival strategy of many pathogenic bacteria.7,8 Not only can single bacteria change their shape, in addition they cooperatively assemble as in the case of streptococci. The assembly process is controlled by enzymatic chain cleavage, which is influenced by many other parameters such as metal ions or bioactive, organic compounds.9 The bacteria assemblies are of fundamental interest, e.g., for the understanding of biofilm formation or its prevention.10 In the case of Bacillus subtilis, the bacteria form linear chains and then larger structures and finally form a biofilm.11,12 Therefore a control over disassembly of the bacteria is highly desirable to prevent biofilm formation. Herein, we describe the synthesis of singular nanoparticle species and their arrangement into chains of several particles via a lock/unlock mechanism based on a chemistry used in bacteria to capture and enrich their iron content. Many methods have been reported using electric fields,13 magnetic fields,14,15 temperature,16 pH change,17,18 entropic or van der Waals interactions,19,20 response to biomolecules,21,22 or deformation by irradiation23 to drive the supraparticular assembly. Unlike these methods and unlike previous reports where the assemblies are mediated by the formation of pH-responsive iron complexes24 or palladium complexes cleavable upon ligand addition,25 we have developed a strategy that relies on a reversible lock/unlock mechanism controlled by a redox reaction. The nanoparticles were designed to display two essential but independent properties: The ability to assemble upon application of an external magnetic field and the lock/unlock © 2014 American Chemical Society
Figure 1. Schematics depicting the assembly/disassembly of the nanoparticles. Supraparticular assembly is achieved upon application of an external magnetic field (I) followed by interparticle locking through cross-linking of the hydroxyamic acid decorated nanoparticles with ferric ions (II). The suprastructure can be reversed to singular nanoparticles by the addition of a reducing agent, e.g., vitamin C, and hence unlocking of the suprastructure (III).
structure directing modules in the nanoparticles to drive the supraparticular assembly. An amount of 66 wt % of magnetite was encapsulated in larger (hydrodynamic diameter 152 ± 65 nm) polystyrene nanoparticles by seeded miniemulsion polymerization (see Supporting Information Figure S1 for TEM images of oleate coated magnetite before and after encapsulation into polystyrene nanoparticles). The locking mechanism was inspired by the formation of polymers by supramolecular chemistry.26,27 One prominent example is described by the addition of salt to a solution containing multicoordinating ligands, leading to the formation of an organometallic complex between the coordinating building blocks summing up to a supramolecular polymer.28 The implementation of the lock/unlock mechanism was achieved by copolymerizing styrene with the synthesized methacrylhydroxamic acid, a comonomer presenting a hydroxyamic functionality. The very high formation constant of hydroxamato-complexes with iron(III) ions (log β3 ∼ 30)20 and the fast complexation kinetics provide predestined properties for Received: December 12, 2013 Revised: January 14, 2014 Published: January 21, 2014 1300
dx.doi.org/10.1021/cm4040769 | Chem. Mater. 2014, 26, 1300−1302
Chemistry of Materials
Communication
revealing the presence of the functional groups on the nanoparticles surface.29 The magnetic properties of the iron oxide/polymer hybrid nanoparticles were investigated via vibrating sample magnetometer (VSM) measurements. The nanoparticles show a superparamagnetic behavior (only minute hysteresis at room temperature) with a saturation magnetization of 49 emu·g−1 (Supporting Information Figure S1). The supraparticular assembly was achieved by passing a controlled flow of nanoparticle dispersions through a static ring magnet. The suprastructure was chemically locked by crosslinking via complex formation with an aqueous solution containing 1 mg·L−1 FeCl3 that was also passed through the static magnet. It is important to carefully control the concentration of iron(III) salt. When the salt concentration is too high (>2 mg·L−1 FeCl3), precipitation due to collapse of the electrostatic stabilization of the nanoparticles is observed. The locked supraparticular structures can be obtained by fast removal of the ring magnet. The size and shape of the obtained suprastructures were evaluated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively (Figure 3). The average hydrodynamic diameter of the locked suprastructure was up to ∼1 μm, i.e., much larger than the initial singular nanoparticles. Most of the nanoparticles were arranged in a
the use of this system as an efficient lock between neighboring particles.29,30 The high capturing affinity of hydroxamates is observed in the form of natural siderophores,31,32 i.e., iron chelating compounds that are produced by bacteria to transport ferric ions.33 In our case, the addition of ferric ions shall ensure an efficient interparticle cross-linking mediated by the bioinspired surface functionalized with hydroxamic acid groups. When reducing the iron(III) to ferrous ions, the complex stability dramatically decreases. The less stable complex is not able to ensure particle cross-linking. An unlocking is hence achieved, and the particles disassemble (Figure 1). In analogy, in bacteria, the hydroxamato-complex of iron(III) is reduced to iron(II) to release the iron from its manacle, the hydroxamic acid ligands.34 The lock/unlock mechanism was first investigated with methacrylhydroxamic acid in aqueous solution. The synthesized methacrylhydroxamic acid was mixed at pH ∼9−10 with a 10 mmol aqueous solution of the hydoxyamic acid and a 5 mmol aqueous solution of FeCl3. A red color appeared instantaneously with an absorption maximum at ∼480 nm identified by UV−vis spectroscopy. The absorption maximum is a result of the hydroxamato-ligand to iron(III)−metal charge transfer.35 The reversibility of the complex formation was verified by adding a 20 mmol vitamin C solution to the iron(III) complex. The color disappeared immediately (Figure 2a). The magnitude of electric charges at the double layer of the poly(styrene-co-methacrylhydroxyamic acid)/magnetite hybrid nanoparticles was monitored as a function of the pH by zeta potential measurements (Figure 2b). A significant decrease of the zeta potential was observed around the pKa of hydroxyamic acids (∼8−9) due to the deprotonation of the acidic group,
Figure 3. (I) Suprapraticular assembly of magnetic nanoparticles (a) in a pseudolinear fashion and locking of the suprastructure by crosslinking with ferric ions to form stable suprastructures (b). (II) Unlocking of the suprastructure by reduction of iron(III) to iron(II) by vitamin C, leading to a disassembly into singular nanoparticles (c).
Figure 2. (a) Absorption spectrum of iron(III) complexed with hydroxamic acid (red curve) and after addition of vitamin C (black curve). (b) Deprotonation of hydroxamic acid functionalized nanoparticles monitored by zeta potential measurements. 1301
dx.doi.org/10.1021/cm4040769 | Chem. Mater. 2014, 26, 1300−1302
Chemistry of Materials
■
linear or pseudolinear fashion in twisted chains of nanoparticles (Figure 3b). Thus, the stable linkage via metal-complexation still allows for a high flexibility of the binding angles between the nanoparticles. The resulting twisted nanoparticle chains highly resemble arrangements of streptococci (Figure S2, Supporting Information). The disassembly or unlocking of the suprastructure was realized by adding 1 g·L−1 of an aqueous vitamin C containing solution and therewith forming a reducing medium. Removal of the interparticle cross-linking and disassembly onto mostly singular entities was shown by TEM and DLS (Figure 3). When aggregating the particles without the presence of a magnet through addition of larger quantities of iron(III) (>10 mg·L−1 FeCl3), the particles form three-dimensional aggregates, owing to a collapse of the electrostatic stabilization. Upon addition of vitamin C, hardly any disassembly can be observed since the particles are not explicitly connected by hydroxamatocomplexes and the reversibility of the linear arrangement is not possible by simply unlocking the complex. Thus, the size of the linear nanoparticles aggregates can be molecularly controlled through complex formation/destruction which is mediated by a redox stimulus for the assembly and disassembly processes, respectively. In conclusion, we have demonstrated a new strategy for the synthesis of nanoparticles displaying supraparticular assemblies mimicking the cooperative arrangement of streptococci bacteria. The magnetic functionality of the nanoparticles was used for the nonpermanent formation of pseudolinear suprastructures. Because the nanoparticles surface was decorated with bioinspired hydroxyamic acid ligands, the obtained structures could be locked by complex formation with ferric ions. By reducing the ferric ions to ferrous ions with vitamin C, the cohesion between individual nanoparticles in the suprastructure becomes loose and singular nanoparticles are recovered. The model system shows the possibility to mimic naturally occurring bacterial assemblies. Since the phagocytosis of particles is inhibited when they display high aspect ratios (>20),36 the concept can be used for applications where the shape of the nanomaterials plays a major role in their performance, i.e., drug-delivery in vivo and cell uptake. The formation of suprastructures can be a strategy to avoid phagocytosis in vivo and release individual nanoparticles as drug-delivery carriers suitable for cell uptake in a reducing medium.
■
REFERENCES
(1) Feynman, R. P. Eng. Sci. 1960, 22−36. (2) Ozin, G. A.; Manners, I.; Fournier-Bidoz, S.; Arsenault, A. Adv. Mater. 2005, 17, 3011−3018. (3) Grzelczak, M.; Vermant, J.; Furst, E. M.; Liz-Marzán, L. M. ACS Nano 2010, 4, 3591−3605. (4) Guo, J.-L.; Chiou, Y.-D.; Liang, W.-I.; Liu, H.-J.; Chen, Y.-J.; Kuo, W.-C.; Tsai, C.-Y.; Tsai, K.-A.; Kuo, H.-H.; Hsieh, W.-F.; Juang, J.-Y.; Hsu, Y.-J.; Lin, H.-J.; Chen, C.-T.; Liao, X.-P.; Shi, B.; Chu, Y.-H. Adv. Mater. 2013, 25, 2040−2044. (5) Whitesides, G. M.; Ismagilov, R. F. Science 1999, 284, 89−92. (6) Young, K. D. Curr. Opin. Microbiol. 2007, 10, 596−600. (7) Justice, S. S.; Hunstad, D. A.; Cegelski, L.; Hultgren, S. J. Nat. Rev. Microbiol. 2008, 6, 162−168. (8) Wollscheid-Lengeling, E.; Kerksiek, K. Infectious Diseases and Aging. www.infection-research.de, 2009. (9) Ekstedt, R. D.; Stollerman, G. H. J. Exp. Med. 1960, 112, 671− 686. (10) Kolodkin-Gal, I.; Cao, S. G.; Chai, L.; Bottcher, T.; Kolter, R.; Clardy, J.; Losick, R. Cell 2012, 149, 684−692. (11) Vlamakis, H.; Chai, Y. R.; Beauregard, P.; Losick, R.; Kolter, R. Nat. Rev. Microbiol. 2013, 11, 157−168. (12) Volfson, D.; Cookson, S.; Hasty, J.; Tsimring, L. S. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 15346−15351. (13) Vutukuri, H. R.; Demirörs, A. F.; Peng, B.; van Oostrum, P. D. J.; Imhof, A.; van Blaaderen, A. Angew. Chem., Int. Ed. 2012, 51, 11249−11253. (14) Bannwarth, M. B.; Kazer, S. W.; Ulrich, S.; Glasser, G.; Crespy, D.; Landfester, K. Angew. Chem., Int. Ed. 2013, 52, 10107−10111. (15) Yuan, J. Y.; Xu, Y. Y.; Muller, A. H. E. Chem. Soc. Rev. 2011, 40, 640−655. (16) Liu, Y. D.; Han, X. G.; He, L.; Yin, Y. D. Angew. Chem., Int. Ed. 2012, 51, 6373−6377. (17) Li, D. X.; He, Q.; Cui, Y.; Li, J. B. Chem. Mater. 2007, 19, 412− 417. (18) Motornov, M.; Roiter, Y.; Tokarev, I.; Minko, S. Prog. Polym. Sci. 2010, 35, 174−211. (19) Liu, K.; Nie, Z. H.; Zhao, N. N.; Li, W.; Rubinstein, M.; Kumacheva, E. Science 2010, 329, 197−200. (20) Bishop, K. J. M.; Wilmer, C. E.; Soh, S.; Grzybowski, B. A. Small 2009, 5, 1600−1630. (21) Hu, J. M.; Zhang, G. Q.; Liu, S. Y. Chem. Soc. Rev. 2012, 41, 5933−5949. (22) Claridge, S. A.; Goh, S. L.; Frechet, J. M. J.; Williams, S. C.; Micheel, C. M.; Alivisatos, A. P. Chem. Mater. 2005, 17, 1628−1635. (23) Zhu, Z. C.; Senses, E.; Akcora, P.; Sukhishvili, S. A. ACS Nano 2012, 6, 3152−3162. (24) Ejima, H.; Richardson, J. J.; Liang, K.; Best, J. P.; van Koeverden, M. P.; Such, G. K.; Cui, J.; Caruso, F. Science 2013, 341, 154−157. (25) Wang, Y.; Hollingsworth, A. D.; Yang, S. K.; Patel, S.; Pine, D. J.; Weck, M. J. Am. Chem. Soc. 2013, 135, 14064−14067. (26) Lehn, J. M. Chem. Soc. Rev. 2007, 36, 151−160. (27) Lehn, J. M. Science 2002, 295, 2400−2403. (28) Brunsveld, L.; Folmer, B. J. B.; Meijer, E. W.; Sijbesma, R. P. Chem. Rev. 2001, 101, 4071−4097. (29) Monzyk, B.; Crumbliss, A. L. J. Am. Chem. Soc. 1979, 101, 6203−6213. (30) Schwarzenbach, G.; Schwarzenbach, K. Helv. Chim. Acta 1963, 46, 1390−&. (31) Miller, M. J. Chem. Rev. 1989, 89, 1563−1579. (32) Codd, R. Coord. Chem. Rev. 2008, 252, 1387−1408. (33) Faraldo-Gomez, J. D.; Sansom, M. S. P. Nat. Rev. Mol. Cell Biol. 2003, 4, 105−116. (34) Rappoport, Z.; Liebman, J. F. The Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids; Wiley: 2008. (35) Dhungana, S.; Harrington, J. M.; Gebhardt, P.; Möllmann, U.; Crumbliss, A. L. Inorg. Chem. 2007, 46, 8362−8371. (36) Champion, J. A.; Mitragotri, S. Pharm. Res. 2009, 26, 244−249.
ASSOCIATED CONTENT
S Supporting Information *
Experimental procedures, characterization data. This material is available free of charge via the Internet at http://pubs.acs.org.
■
Communication
AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. Notes
The authors declare no competing financial interests.
■
ACKNOWLEDGMENTS M.B.B. is a recipient of a fellowship funded through the Excellence Initiative (DFG/GSC 266). Peter Happ is acknowledged for helpful discussions. 1302
dx.doi.org/10.1021/cm4040769 | Chem. Mater. 2014, 26, 1300−1302
