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  • Publication
    Understanding intracellular nanoparticle trafficking fates through spatiotemporally resolved magnetic nanoparticle recovery
    The field of nanomedicine has the potential to be a game-changer in global health, with possible applications in prevention, diagnostics, and therapeutics. However, despite extensive research focus and funding, the forecasted explosion of novel nanomedicines is yet to materialize. We believe that clinical translation is ultimately hampered by a lack of understanding of how nanoparticles really interact with biological systems. When placed in a biological environment, nanoparticles adsorb a biomolecular layer that defines their biological identity. The challenge for bionanoscience is therefore to understand the evolution of the interactions of the nanoparticle–biomolecules complex as the nanoparticle is trafficked through the intracellular environment. However, to progress on this route, scientists face major challenges associated with isolation of specific intracellular compartments for analysis, complicated by the diversity of trafficking events happening simultaneously and the lack of synchronization between individual events. In this perspective article, we reflect on how magnetic nanoparticles can help to tackle some of these challenges as part of an overall workflow and act as a useful platform to investigate the bionano interactions within the cell that contribute to this nanoscale decision making. We discuss both established and emerging techniques for the magnetic extraction of nanoparticles and how they can potentially be used as tools to study the intracellular journey of nanomaterials inside the cell, and their potential to probe nanoscale decision-making events. We outline the inherent limitations of these techniques when investigating particular bio-nano interactions along with proposed strategies to improve both specificity and resolution. We conclude by describing how the integration of magnetic nanoparticle recovery with sophisticated analysis at the single-particle level could be applied to resolve key questions for this field in the future.
      148Scopus© Citations 6
  • Publication
    Differential Recognition of Nanoparticle Protein Corona and Modified Low-Density Lipoprotein by Macrophage Receptor with Collagenous Structure
    Key practical challenges such as understanding the immunological processes at the nanoscale and controlling the targeting and accumulation of nano-objects in vivo now further stimulate efforts to underpin phenomenological knowledge of the nanoscale with more mechanistic and molecular insight. Thus, the question as to what constitutes nanoscale biological identity continues to evolve. Certainly nanoparticles in contact with a complex biological milieu develop a biological identity, differing from the original nanomaterial, now referred to as the "biomolecular corona". However, this surface-adsorbed layer of biomolecules may in some circumstance lead to different forms of receptor-particle interactions not evident only from the identity of the surface-adsorbed biomolecules and hard to predict or detect by current physicochemical methods. Here we show that scavenger receptors may recognize complex as yet unidentified biomolecular surface layer motifs, even when no current physicochemical analysis is capable of doing so. For instance, fluorescently labeled SiO nanoparticles in a biological milieu are strongly recognized by the macrophage receptor with collagenous structure (MARCO) in even dense biological media (human serum) apparently using a form of binding with which most of the MARCO's known ligands (e.g., LPS, modified LDL) fail to compete. Such observations may suggest the need for a much stronger emphasis on nanoscale receptor-corona and other biomolecular interaction studies if one wishes to unravel how biomolecular recognition drives outcomes in the nanoscale biological domain. 2
    Scopus© Citations 61  117