Caco-2 Cell Acquisition of Dietary Iron(III) Invokes a Nanoparticulate Endocytic Pathway

Pereira, Dora I. A.; Mergler, Bianca I.; Faria, Nuno; Bruggraber, Sylvaine F. A.; Aslam, Mohamad F.; Poots, Lynsey K.; Prassmayer, Laura; Lönnerdal, Bo; Brown, Andy; Powell, Jonathan J.

doi:10.1371/journal.pone.0081250

Cited by 61 publications

(75 citation statements)

References 74 publications

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“…One of the most innovative preparation is "sucrosomial" iron (SI), that is a source of ferric pyrophosphate covered by phospholipids plus sucrose esters of fatty acids matrix [84]. In vitro experiments on human intestinal Caco-2 cells suggest that SI could be taken up through a DMT-1 independent mechanism [84], possibly through endocytosis and similarly to what happens with nanoparticles [85,86] (see below). Whether this occurs also in vivo, as well as whether SI utilizes unique mechanisms also to enter the bloodstream remain to be proven.…”

Section: New Preparationsmentioning

confidence: 99%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

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Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

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Section: New Preparationsmentioning

confidence: 99%

Modern iron replacement therapy: clinical and pathophysiological insights

et al. 2017

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“…Powell showed data from recent studies demonstrating that nano-Fe 3þ crosses the apical surface of Caco-2 cells via an endocytic pathway before being dissolved in endosomes or lysosomes inside the cell (figure 5), and that its subsequent homeostasis is under the normal regulatory control of dietary iron absorption, namely via ferroportin-dependent efflux from enterocytes. This suggests that nano-Fe 3þ thus offers potential as a novel oral iron supplement with enhanced uptake in the nano form followed by release and processing in the body via the normal soluble iron pathway [25]. Also approaching the topic from a clinical perspective, Andre Nel (University of California, Los Angeles) discussed existing data that supports predictive modelling and alternative testing strategies for regulatory decision making regarding nanomaterials.…”

Section: (D) Interactions Of Nanomaterials With the Human Body: Nanosmentioning

confidence: 99%

‘Bio-nano interactions: new tools, insights and impacts’: summary of the Royal Society discussion meeting

Lynch

Feitshans

Kendall

2015

Phil. Trans. R. Soc. B

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Bio-nano interactions can be defined as the study of interactions between nanoscale entities and biological systems such as, but not limited to, peptides, proteins, lipids, DNA and other biomolecules, cells and cellular receptors and organisms including humans. Studying bio-nano interactions is particularly useful for understanding engineered materials that have at least one dimension in the nanoscale. Such materials may consist of discrete particles or nanostructured surfaces. Much of biology functions at the nanoscale; therefore, our ability to manipulate materials such that they are taken up at the nanoscale, and engage biological machinery in a designed and purposeful manner, opens new vistas for more efficient diagnostics, therapeutics (treatments) and tissue regeneration, so-called nanomedicine. Additionally, this ability of nanomaterials to interact with and be taken up by cells allows nanomaterials to be used as probes and tools to advance our understanding of cellular functioning. Yet, as a new technology, assessment of the safety of nanomaterials, and the applicability of existing regulatory frameworks for nanomaterials must be investigated in parallel with development of novel applications. The Royal Society meeting 'Bio-nano interactions: new tools, insights and impacts' provided an important platform for open dialogue on the current state of knowledge on these issues, bringing together scientists, industry, regulatory and legal experts to concretize existing discourse in science law and policy. This paper summarizes these discussions and the insights that emerged. Background to the meetingThroughout the 21st century, reports about dangers and benefits of using well-established toxins, as well as substances that were previously considered innocuous, have been diligently examined by the Royal Society. The Royal Society has proactively engaged in discussions regarding nanotechnologies since the early 2000s. It was the first major international scientific community to publish its opinion regarding the opportunities and challenges posed by nanotechnologies and nanomaterials for society [1]. As noted in the Royal Society's report in 2004, nanotechnology offers a fresh perspective for scientific understanding of the physical properties of matter. Subsequently, Royal Society journals have published pioneering articles concerning this emerging field, starting with inhalation toxicology and exploring scientific concerns that ultrafine airborne particles might cause harmful effects (figure 1), and the implications of that possible harm when applying nanotechnology in a diverse range of consumer applications [2]. Those findings prompted a pause to reconsider the overwhelmingly positive attitudes regarding the 'nanotechnology revolution'. Thus, although potential dangers from substances used in nanomedicine are unquantified as yet, both the potential benefits of applications and any possible negative implications following their use have consistently been the subject of lively discourse at the Royal Society.On 3...

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“…For example, Jahn et al (2011) studied the uptake of hemin-coupled iron hydroxide NPs on Caco-2 cells and they speculated a strong effect due to the colloidal stability of such NPs in the medium, but they did not perform any stability study. Pereira et al (2013) found that Fe(III)-oxo hydroxide NPs forms ferrihydrite-like complexes after a simulated in vitro digestion. PC NPs could not be isolated from GI fluids without aggregation, but they used the approach to synthesize ferrihydrite complexes ex novo for studying their biological response on Caco-2 cells, bypassing the isolation of such NPs from digestive fluids.…”

Section: Stability Of Nps In Simulated Gastrointestinal Fluidsmentioning

confidence: 96%

Effect of protein corona magnetite nanoparticles derived from bread in vitro digestion on Caco-2 cells morphology and uptake

Silvio

Rigby

Bajka

et al. 2016

The International Journal of Biochemistry & Cell Biology

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Nanoparticles (NPs) in biological fluids immediately interact with proteins forming a biomolecular corona (PC) that imparts their biological identity. While several studies on the formation of the PC in human plasma have been reported, the PC of orally administrated NPs has been less investigated, mostly in the presence of a food matrix. In fact, food matrixes when digested are subject of several dynamic changes that will certainly affect the PC formed on the NPs. The lack of studies on this topic is clearly related to the difficulty in isolating representative PC NPs from such a complex environment. In this work magnetite NPs were added to in vitro simulated digestion simultaneously with bread and PC NPs were isolated after gastric and duodenal phases by sucrose gradient ultracentrifugation (UC). The PC NPs were characterized in terms of size and protein composition. Translocation studies were then performed on Caco-2 monolayers in a serum free environment and cell morphology was characterized by confocal microscopy. PC NPs isolated from gastric and duodenal phases were different in size, surface charge and protein corona composition. NP cellular uptake was enhanced by the digestive PC inducing morphology changes in the cell monolayer. Overall, in this work we were able to isolate PC NPs from digested fluids in the presence of a food matrix and study their biological response on Caco-2 cells.

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Caco-2 Cell Acquisition of Dietary Iron(III) Invokes a Nanoparticulate Endocytic Pathway

Cited by 61 publications

References 74 publications

Modern iron replacement therapy: clinical and pathophysiological insights

Modern iron replacement therapy: clinical and pathophysiological insights

‘Bio-nano interactions: new tools, insights and impacts’: summary of the Royal Society discussion meeting

Effect of protein corona magnetite nanoparticles derived from bread in vitro digestion on Caco-2 cells morphology and uptake

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