Browsing by Author "Moghimi, S. M."

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    AFM visualization of sub-50nm polyplex disposition to the nuclear pore complex without compromising the integrity of the nuclear envelope
    (Elsevier, 2016-11-11) Andersen, Helene; Parhamifar, Laden; Hunter, Alan Christy; Shahin, Victor; Moghimi, S. M.
    It has been questioned as to whether polyplexes in the cytoplasm can reach the nuclear compartment and if so in what form. By applying atomic force microscopy (AFM) to the nuclear envelope and the nuclear pore complexes, we demonstrate that disposition of polyethylenimine (PEI)/DNA polyplexes that were microinjected into the oocytes of Xenopus laevis, as an example of a non-dividing cell, is exclusive to the nuclear pore complex (NPC). AFM images show NPCs clogged only with sub-50 nm polyplexes. This mode of disposition neither altered the morphology/integrity of the nuclear membrane nor the NPC. AFM images further show polyplexes on the nucleoplasmic side of the envelope, presumably indicating species in transit. Transmission electron microscopy studies of ruptured nuclei from transfected human cell lines demonstrate the presence of sub-50 nm particles resembling polyplexes in morphology compared with control preparations.
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    Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes
    (Nature, 2017-05-03) Wibroe, Peter P.; Anselmo, Aaron C.; Nilsson, Per H.; Gupta, Vivek; Urbanics, Rudolf; Szebeni, Janos; Hunter, Alan Christy; Mitragotri, Samir; Mollnes, Tom Eirik; Moghimi, S. M.
    Intravenously injected nanopharmaceuticals induce adverse cardiopulmonary reactions in sensitive human subjects and these reactions are reproducible in pigs. The underlying mechanisms are poorly understood, but a role for both the complement system and reactive macrophages has been implicated. Here we show the dominance and importance of early pulmonary intravascular macrophage clearance kinetics in adverse particle-mediated cardiopulmonary distress in pigs and irrespective of complement activation. Delaying particle recognition by macrophages within the first few minutes of injection overcome adverse reactions in pigs. This was achieved by two independent approaches: (i) changing particle geometry from a spherical shape (which trigger cardiopulmonary distress) to either rod- or disk-shape morphology and (ii) by physically adhering spheres to the surface of erythrocytes. These approaches bypasses particle surface engineering approaches to prevent robust macrophage recognition as well as the use of immunological or pharmacological modulators to reduce/overcome nanomedicine related adverse cardiopulmonary distress.
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    New platforms for multi-functional ocular lenses: engineering double-sided functionalized nano-coatings
    (Taylor and Francis, 2015-01-13) Mehta, P.; Justo, L.; Walsh, Susannah E.; Arshad, M. S.; Wilson, C. G.; O'Sullivan, C. K.; Moghimi, S. M.; Vizirianakis, I. S.; Avgoustakis, K.; Fatouros, D. G.; Ahmad, Z.