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      Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery

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          Abstract

          In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.

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          Most cited references 131

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          Progress in applications of magnetic nanoparticles in biomedicine

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            Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis.

            The relatively high transfection efficiency of polyethylenimine (PEI) vectors has been hypothesized to be due to their ability to avoid trafficking to degradative lysosomes. According to the proton sponge hypothesis, the buffering capacity of PEI leads to osmotic swelling and rupture of endosomes, resulting in the release of the vector into the cytoplasm. The mechanism of PEI-mediated DNA transfer was investigated using quantitative methods to study individual steps in the overall transfection process. In addition to transfection efficiency, the cellular uptake, local pH environment, and stability of vectors were analyzed. N-Quaternized (and therefore non-proton sponge) versions of PEI and specific cell function inhibitors were used to further probe the proton sponge hypothesis. Both N-quaternization and the use of bafilomycin A1 (a vacuolar proton pump inhibitor) reduced the transfection efficiency of PEI by approximately two orders of magnitude. Chloroquine, which buffers lysosomes, enhanced the transfection efficiency of N-quaternized PEIs and polylysine by 2-3-fold. In contrast, chloroquine did not improve the transfection efficiency of PEI. The measured average pH environment of PEI vectors was 6.1, indicating that they successfully avoid trafficking to acidic lysosomes. Significantly lower average pH environments were observed for permethyl-PEI (pH 5.4), perethyl-PEI (pH 5.1), and polylysine (pH 4.6) vectors. Cellular uptake levels of permethyl-PEI and perethyl-PEI vectors were found to be 20 and 90% higher, respectively, than that of parent PEI vectors, indicating that the reduction in transfection activity of the N-quaternized PEIs is due to a barrier downstream of cellular uptake. A polycation/DNA-binding affinity assessment showed that the more charge dense N-quaternized PEIs bind DNA less tightly than PEI, demonstrating that poor vector unpackaging was not responsible for the reduced transfection activity of the N-quaternized PEIs. The results obtained are consistent with the proton sponge hypothesis and strongly suggest that the transfection activity of PEI vectors is due to their unique ability to avoid acidic lysosomes. Copyright (c) 2004 John Wiley & Sons, Ltd.
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              Magnetic nanoparticles for drug delivery

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                10 April 2015
                April 2015
                : 16
                : 4
                : 8070-8101
                Affiliations
                [1 ]Departament de Fisicoquímica; Facultat de Farmàcia; Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain; E-Mail: mabusquetsvinas@ 123456ub.edu
                [2 ]Departament de Farmàcia i Tecnologia Farmacèutica, Facultat de Farmàcia, Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain; E-Mail: eescribano@ 123456ub.edu
                [3 ]Departament de Fisiologia, Facultat de Farmàcia; Institut de Nanociència i Nanotecnologia (IN2UB), Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain; E-Mail: josepqueralt@ 123456ub.edu
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: joanestelrich@ 123456ub.edu ; Tel.: +34-93-402-4559; Fax: +34-93-403-5987.
                Article
                ijms-16-08070
                10.3390/ijms16048070
                4425068
                25867479
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

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