Improvement of solubility and biocompatibility of MnO based nanoparticles in aqueous solutions
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Improvement of solubility and biocompatibility of MnO based nanoparticles in aqueous solutions Kerstin Koll1, Thomas D. Schladt2,Stefan Weber3, Florian D. Jochum4, Patrick Theato4, Laura M. Schreiber3, Wolfgang Tremel1 1
Institut für anorganische und analytische Chemie, Johannes-Gutenberg Universität, Duesbergweg 10-14, 55099 Mainz, Germany 2 IBM Almaden Research Center, San Jose, CA 95120-6099 TN 37831-6376, U.S.A. 3 Institut für medizinische Physik, Klinik und Polyklinik für diagnostische und interventionelle Radiologie, Universitätsklinikum Mainz (Germany) 4 Institut für organische Chemie, Johannes Gutenberg-Universität Mainz (Germany) ABSTRACT MnO nanoparticles were surface modified using two different multifunctional polymers. By introducing a PEG group, the long term stability, MRI applicability and sterile filtration could be greatly improved. Furthermore, PEGylated MnO NPs were less toxic compared to nonPEGylated NPs. The results suggest that these nanoparticles are suitable for in vivo applications. INTRODUCTION Nanoparticles (NPs) have gained enormous interest in the biomedical world. Numerous examples such as tissue engineering, disease detection and drug targeting1,2 can be found in the literature. Here, magnetic NPs are of special interest, since the magnetic core itself can be modified e.g. for protein separation3 or as MRI contrasting agents4. For the latter application, iron oxide NPs dominate the market as T2, or “negative” contrast agents. On the other hand, typical T1, or “positive” agents comprise metal-organic Gd-complexes. However, recently MnO NPs also showed promising results in this respect5. Most magnetic NPs are hydrophobic in nature and therefore need to be surface modified to allow solubility in aqueous solution. For this purpose, different strategies are known1,6 , the most applied method being the use of polymers7,8,9 . These have the advantage that additional functional groups can be introduced, further improving the magnetic core. However, the choice of the polymer is essential since biocompatibility needs to be guaranteed. Poly-(ethylene glycol) (PEG) is possibly the most prominent polymer. Already approved by the FDA, numerous drugs functionalized with PEG have entered clinical trials10. The major advantage of PEG is that drugs modified with this polymer allow a prolonged circulation in the patient by escaping the human immune system. Thereby, the concentration of the applied drug can be lowered, decreasing toxic side effects. We have designed MnO nanoparticles11 by previously described methods and surface modified them with the use of a multifunctional polymer (Poly1)12. This polymer features an anchoring group (dopamine, DA) to bind to the metal oxide surface, a fluorescence dye (NBD) and free amino groups to allow further functionalization (1,4-diaminobutane). Additionally, MnO NPs were surface functionalized with a polymer in which PEG groups were further introduced (PEG-Poly)13. Both polymer functionalized NPs were compared in terms of long-term stability in body fluids, MRI
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