Open Access
Issue
Published:
10 November 2010
Preparation and Control of the Formation of Single Core and Clustered Nanoparticles for Biomedical Applications Using a Versatile Amphiphilic Diblock Copolymer
)
Download citation
559
Views
23
Downloads
31
Crossref
N/A
WoS
33
Scopus
0
CSCD
We report the application of a versatile diblock copolymer, poly(ethylene oxide)-b-poly(γ-methacryloxypropyl trimethoxysilane) (PEO-b-PγMPS), to prepare nanocrystals such as iron oxide nanoparticles or quantum dots, with either a single core or multi-core cluster, for biomedical applications. This amphiphilic copolymer comprises both a hydrophilic PEO segment and a hydrophobic segment with a "surface anchoring moiety" (the silane group) which can interact effectively with the hydrophobic nanocrystals through ligand exchange. One of the unique features of this work is that we can control the formation of either single core nanoparticles or multi-core nanoclusters by simply varying the conditions of ligand exchange and aging of the mixture of block copolymer and nanoparticles without needing to change the copolymer. The morphologies of the resulting single core nanoparticles or multi-core nanoclusters were confirmed by dynamic light scattering and transmission electron microscopy. The clustered nanoparticles exhibit enhanced physicochemical properties that are beyond those expected from a simple accumulation of individual nanoparticles. Additionally, the hybrid nanoparticles containing both magnetic iron oxide nanoparticles and optical quantum dots obtained using our strategy provide have combined magnetic and optical functionalities that allow for potential new and expanded biomedical applications, as demonstrated by their use for magnetic resonance imaging and biomarker-targeted cell imaging.
menu
Preparation and Control of the Formation of Single Core and Clustered Nanoparticles for Biomedical Applications Using a Versatile Amphiphilic Diblock Copolymer
)
Abstract
We report the application of a versatile diblock copolymer, poly(ethylene oxide)-b-poly(γ-methacryloxypropyl trimethoxysilane) (PEO-b-PγMPS), to prepare nanocrystals such as iron oxide nanoparticles or quantum dots, with either a single core or multi-core cluster, for biomedical applications. This amphiphilic copolymer comprises both a hydrophilic PEO segment and a hydrophobic segment with a "surface anchoring moiety" (the silane group) which can interact effectively with the hydrophobic nanocrystals through ligand exchange. One of the unique features of this work is that we can control the formation of either single core nanoparticles or multi-core nanoclusters by simply varying the conditions of ligand exchange and aging of the mixture of block copolymer and nanoparticles without needing to change the copolymer. The morphologies of the resulting single core nanoparticles or multi-core nanoclusters were confirmed by dynamic light scattering and transmission electron microscopy. The clustered nanoparticles exhibit enhanced physicochemical properties that are beyond those expected from a simple accumulation of individual nanoparticles. Additionally, the hybrid nanoparticles containing both magnetic iron oxide nanoparticles and optical quantum dots obtained using our strategy provide have combined magnetic and optical functionalities that allow for potential new and expanded biomedical applications, as demonstrated by their use for magnetic resonance imaging and biomarker-targeted cell imaging.
References(44)
Kim, J.; Piao, Y.; Hyeon, T. Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. Chem. Soc. Rev. 2009, 38, 372–390.
Laurent, S.; Forge, D.; Port, M.; Roch, A.; Robic, C.; Elst, L. V.; Muller, R. N. Magnetic iron oxide nanoparticles: Synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 2008, 108, 2064–2110.
Douma, K.; Prinzen, L.; Slaaf, D. W.; Reutelingsperger, C. P. M.; Biessen, E. A. L.; Hackeng, T. M.; Post, M. J.; van Zandvoort, M. A. M. J. Nanoparticles for optical molecular imaging of atherosclerosis. Small 2009, 5, 544–557.
Murray, C. B.; Norris, D. J.; Bawendi, M. G. Synthesis and characterization of nearly monodisperse CdE (E = S, Se, Te) semiconductor nanocrystallites. J. Am. Chem. Soc. 1993, 115, 8706–8715.
De Palma, R.; Peeters, S.; Van Bael, M. J.; Van den Rul, H.; Bonroy, K.; Laureyn, W.; Mullens, J.; Borghs, G.; Maes, G. Silane ligand exchange to make hydrophobic superparamagnetic nanoparticles water-dispersible. Chem. Mater. 2007, 19, 1821–1831.
Jun, Y. W.; Huh, Y. M.; Choi, J. S.; Lee, J. H.; Song, H. T.; Kim, S.; Yoon, S.; Kim, K. S.; Shin, J. S.; Suh, J. S.; Cheon, J. Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. J. Am. Chem. Soc. 2005, 127, 5732–5733.
Hezinger, A. F. E.; Tessmar, J.; Gopferich, A. Polymer coating of quantum dots—A powerful tool toward diagnostics and sensorics. Eur. J. Pharm. Biopharm. 2008, 68, 138–152.
Park, J.; Yu, M. K.; Jeong, Y. Y.; Kim, J. W.; Lee, K.; Phan, V. N.; Jon, S. Antibiofouling amphiphilic polymer-coated superparamagnetic iron oxide nanoparticles: Synthesis, characterization, and use in cancer imaging in vivo. J. Mater. Chem. 2009, 19, 6412–6417.
Gao, X. H.; Cui, Y. Y.; Levenson, R. M.; Chung, L. W. K.; Nie, S. M. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 2004, 22, 969–976.
Pellegrino, T.; Manna, L.; Kudera, S.; Liedl, T.; Koktysh, D.; Rogach, A. L.; Keller, S.; Radler, J.; Natile, G.; Parak, W. J. Hydrophobic nanocrystals coated with an amphiphilic polymer shell: A general route to water soluble nanocrystals. Nano Lett. 2004, 4, 703–707.
Lee, H.; Lee, E.; Kim, D. K.; Jang, N. K.; Jeong, Y. Y.; Jon, S. Antibiofouling polymer-coated superparamagnetic iron oxide nanoparticles as potential magnetic resonance contrast agents for in vivo cancer imaging. J. Am. Chem. Soc. 2006, 128, 7383–7389.
Ai, H.; Flask, C.; Weinberg, B.; Shuai, X.; Pagel, M. D.; Farrell, D.; Duerk, J.; Gao, J. M. Magnetite-loaded polymeric micelles as ultrasensitive magnetic-resonance probes. Adv. Mater. 2005, 17, 1949–1952.
Nasongkla, N.; Bey, E.; Ren, J. M.; Ai, H.; Khemtong, C.; Guthi, J. S.; Chin, S. F.; Sherry, A. D.; Boothman, D. A.; Gao, J. M. Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett. 2006, 6, 2427–2430.
Kim, B. S.; Taton, T. A. Multicomponent nanoparticles via self-assembly with cross-linked block copolymer surfactants. Langmuir 2007, 23, 2198–2202.
Kim, B. S.; Qiu, J. M.; Wang, J. P.; Taton, T. A. Magneto-micelles: Composite nanostructures from magnetic nanoparticles and cross-linked amphiphilic block copolymers. Nano Lett. 2005, 5, 1987–1991.
Euliss, L. E.; Grancharov, S. G.; O'Brien, S.; Deming, T. J.; Stucky, G. D.; Murray, C. B.; Held, G. A. Cooperative assembly of magnetic nanoparticles and block copolypeptides in aqueous media. Nano Lett. 2003, 3, 1489–1493.
Zhang, L.; Lin, J.; Lin, S. Self-assembly behavior of amphiphilic block copolymer/nanoparticle mixture in dilute solution studied by self-consistent-field theory/density functional theory. Macromolecules 2007, 40, 5582–5592.
Neuberger, T.; Schopf, B.; Hofmann, H.; Hofmann, M.; von Rechenberg, B. Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system. J. Magn. Magn. Mater. 2005, 293, 483–496.
Gao, J. H.; Zhang, B.; Gao, Y.; Pan, Y.; Zhang, X. X.; Xu, B. Fluorescent magnetic nanocrystals by sequential addition of reagents in a one-pot reaction: A simple preparation for multifunctional nanostructures. J. Am. Chem. Soc. 2007, 129, 11928–11935.
Chen, H. W.; Wang, L. Y.; Yeh, J.; Wu, X. Y.; Cao, Z. H.; Wang, Y. A.; Zhang, M. M.; Yang, L.; Mao, H. Reducing non-specific binding and uptake of nanoparticles and improving cell targeting with an antifouling PEO-b-PγMPS copolymer coating. Biomaterials 2010, 31, 5397–5407.
Yu, W. W.; Falkner, J. C.; Yavuz, C. T.; Colvin, V. L. Synthesis of monodisperse iron oxide nanocrystals by thermal decomposition of iron carboxylate salts. Chem. Commun. 2004, 2306–2307.
Li, J. J.; Wang, Y. A.; Guo, W. Z.; Keay, J. C.; Mishima, T. D.; Johnson, M. B.; Peng, X. G. Large-scale synthesis of nearly monodisperse CdSe/CdS core/shell nanocrystals using air-stable reagents via successive ion layer adsorption and reaction. J. Am. Chem. Soc. 2003, 125, 12567–12575.
Chen, H. W.; Wu, X. Y.; Duan, H. W.; Wang, Y. A.; Wang, L. Y.; Zhang, M. M.; Mao, H. Biocompatible polysiloxane-containing diblock copolymer PEO-b-PγMPS for coating magnetic nanoparticles. ACS Appl. Mater. Interf. 2009, 1, 2134–2140.
Atkins, R. C. Colorimetric determination of iron in vitamin supplement tablets. A general chemistry experiment. J. Chem. Educ. 1975, 52, 550–550.
Lalatonne, Y.; Richardi, J.; Pileni, M. P. Van der Waals versus dipolar forces controlling mesoscopic organizations of magnetic nanocrystals. Nat. Mater. 2004, 3, 121–125.
Luttinger, J. M.; Tisza, L. Theory of dipole interaction in crystals. Phys. Rev. 1946, 70, 954–964.
Seo, S. B.; Yang, J.; Lee, T. I.; Chung, C. H.; Song, Y. J.; Suh, J. S.; Yoon, H. G.; Huh, Y. M.; Haam, S. Enhancement of magnetic resonance contrast effect using ionic magnetic clusters. J. Colloid Interf. Sci. 2008, 319, 429–434.
Berret, J. F.; Schonbeck, N.; Gazeau, F.; El Kharrat, D.; Sandre, O.; Vacher, A.; Airiau, M. Controlled clustering of superparamagnetic nanoparticles using block copolymers: Design of new contrast agents for magnetic resonance imaging. J. Am. Chem. Soc. 2006, 128, 1755–1761.
Matsumoto, Y.; Jasanoff, A. T2 relaxation induced by clusters of superparamagnetic nanoparticles: Monte Carlo simulations. Magn. Reson. Imaging 2008, 26, 994–998.
Larsen, B. A.; Haag, M. A.; Serkova, N. J.; Shroyer, K. R.; Stoldt, C. R. Controlled aggregation of superparamagnetic iron oxide nanoparticles for the development of molecular magnetic resonance imaging probes. Nanotechnology 2008, 19, 265102.
Duan, H. W.; Kuang, M.; Wang, X. X.; Wang, Y. A.; Mao, H.; Nie, S. M. Reexamining the effects of particle size and surface chemistry on the magnetic properties of iron oxide nanocrystals: New insights into spin disorder and proton relaxivity. J. Phys. Chem. C 2008, 112, 8127–8131.
Lee, J. H.; Jun, Y. W.; Yeon, S. I.; Shin, J. S.; Cheon, J. Dual-mode nanoparticle probes for high-performance magnetic resonance and fluorescence imaging of neuroblastoma. Angew. Chem. Int. Ed. 2006, 45, 8160–8162.
Barick, K. C.; Aslam, M.; Lin, Y. P.; Bahadur, D.; Prasad, P. V.; Dravid, V. P. Novel and efficient MR active aqueous colloidal Fe3O4 nanoassemblies. J. Mater. Chem. 2009, 19, 7023–7029.
Yang, J.; Dave, S. R.; Gao, X. H. Quantum dot nanobarcodes: Epitaxial assembly of nanoparticle–polymer complexes in homogeneous solution. J. Am. Chem. Soc. 2008, 130, 5286–5292.
Dagata, J. A.; Farkas, N.; Dennis, C. L.; Shull, R. D.; Hackley, V. A.; Yang, C.; Pirollo, K. F.; Chang, E. H. Physical characterization methods for iron oxide contrast agents encapsulated within a targeted liposome-based delivery system. Nanotechnology 2008, 19, 305101.
Goya, G. F.; Berquo, T. S.; Fonseca, F. C.; Morales, M. P. Static and dynamic magnetic properties of spherical magnetite nanoparticles. J. Appl. Phys. 2003, 94, 3520–3528.
Han, D. H.; Wang, J. P.; Luo, H. L. Crystallite size effect on saturation magnetization of fine ferrimagnetic particles. J. Magn. Magn. Mater. 1994, 136, 176–182.
Hadjipanayis, C. G.; Bonder, M. J.; Balakrishanan, S.; Wang, X.; Mao, H.; Hadjipanayis, G. C. Metallic iron nanoparticles for MRI contrast enhancement and local hyperthermia. Small 2008, 4, 1925–1929.
Kim, J.; Piao, Y.; Lee, N.; Park, Y. I.; Lee, I. H.; Lee, J. H.; Paik, S. R.; Hyeon, T. Magnetic nanocomposite spheres decorated with NiO nanoparticles for a magnetically recyclable protein separation system. Adv. Mater. 2010, 22, 57–60.
Gu, H. W.; Ho, P. L.; Tsang, K. W. T.; Wang, L.; Xu, B. Using biofunctional magnetic nanoparticles to capture vancomycin-resistant enterococci and other Gram-positive bacteria at ultralow concentration. J. Am. Chem. Soc. 2003, 125, 15702–15703.
Yi, D. K.; Selvan, S. T.; Lee, S. S.; Papaefthymiou, G. C.; Kundaliya, D.; Ying, J. Y. Silica-coated nanocomposites of magnetic nanoparticles and quantum dots. J. Am. Chem. Soc. 2005, 127, 4990–4991.
Kim, J.; Lee, J. E.; Lee, J.; Jang, Y.; Kim, S. W.; An, K.; Yu, J. H.; Hyeon, T. Generalized fabrication of multifunctional nanoparticle assemblies on silica spheres. Angew. Chem. Int. Ed. 2006, 45, 4789–4793.
Mulder, W. J. M.; Koole, R.; Brandwijk, R. J.; Storm, G.; Chin, P. T. K.; Strijkers, G. J.; de Mello Donegá, C. M.; Nicolay, K.; Griffioen, A. W. Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Lett. 2006, 6, 1–6.
Gao, J. H.; Gu, H. W.; Xu, B. Multifunctional magnetic nanoparticles: Design, synthesis, and biomedical applications. Acc. Chem. Res. 2009, 42, 1097–1107.
Publication history
Copyright
Acknowledgements
The authors wish to thank the staff members of the Robert P. Apkarian Integrated Electron Microscopy Core for their assistance with the electron microscopy work. This work is supported in part by the Emory Molecular Translational Imaging Center with an
Rights and permissions
This article is published with open access at Springerlink.com
This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
FEEDBACK 
TOP