Exploring Primary Liver Macrophages for Studying Quantum Dot Interactions with Biological Systems

Fischer, Hadas D.; Hauck, Tanya S.; Gómez‐Aristizábal, Alejandro; Chan, Warren C. W.

doi:10.1002/adma.200904231

Cited by 74 publications

(67 citation statements)

References 33 publications

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“…2 The intracellular disposition of NMs in these macrophages via, eg, intracellular uptake, exocytosis, and intercellular transport determines the retention time of NMs in the MPS and, thus, their clearance from the body. 3,4 Therefore, studies in this aspect are crucial for the clinical safety of NMs and for developing NMs that can be retained in the body for appropriate times to treat various ailments.…”

Section: Introductionmentioning

confidence: 99%

Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

Jiang¹,

Wang²,

Webster³

et al. 2017

IJN

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Biodegradable nanomaterials have been widely used in numerous medical fields. To further improve such efforts, this study focused on the intracellular disposition of chitosan nanoparticles (CsNPs) in macrophages, a primary cell of the mononuclear phagocyte system (MPS). Such interactions with the MPS determine the nanoparticle retention time in the body and consequently play a significant role in their own clinical safety. In this study, various dye-labeled CsNPs (about 250 nm) were prepared, and a murine macrophage cell line (RAW 264.7) was selected as a model macrophage. The results showed two mechanisms of macrophage incorporation of CsNPs, ie, a clathrin-mediated endocytosis pathway (the primary) and phagocytosis. Following internalization, the particles partly dissociated in the cells, indicating cellular digestion of the nanoparticles. It was proved that, after intracellular uptake, a large proportion of CsNPs were exocytosed within 24 h; this excretion induced a decrease in fluorescence intensity in cells by 69%, with the remaining particles possessing difficulty being cleared. Exocytosis could be inhibited by both wortmannin and vacuolin-1, indicating that CsNP uptake was mediated by lysosomal and multivesicular body pathways, and after exocytosis, the reuptake of CsNPs by neighboring cells was verified by further experiments. This study, thus, elucidated the fate of CsNPs in macrophages as well as identified cellular disposition mechanisms, providing the basis for how CsNPs are recognized by the MPS; such information is crucial to numerous medical applications of CsNPs.

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Section: Introductionmentioning

confidence: 99%

Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

Jiang¹,

Wang²,

Webster³

et al. 2017

IJN

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“…Additional bioassays can be designed and performed for signaling apoptosis and cell death mechanisms involved in nanotoxicity using specific biomarkers (eg, annexin/propidium iodide) but not directly accessing the real-time concentration of metal cation species "free" at the micro-nanoenvironment. Multiple cell-nanoparticle interactions occur at these complex and dynamic biointerfaces, which have been the subject of intense research reported in the literature [43][44][45][46]51,52 and is beyond the focus of this study. Nonetheless, according to the most recent comprehensive review so far addressing the toxicity of QDs published by Oh et al, 9 .50% of articles evaluated the toxicity of Cd-containing QDs using MTT cell viability assay.…”

mentioning

confidence: 99%

“…If toxic cores of QDs (eg, Cd 2+ ) are released into the cytosol, they can elicit biological responses by disrupting mitochondrial function, producing reactive oxygen species and activating the oxidative stress-mediated signaling cascade, leading to apoptosis and cell death. [44][45][46] Moreover, B-cell lymphoma overexpresses metallothionein (MT; low molecular weight 6-7 kDa), a metal-binding protein of animal kingdom that is induced at the transcriptional level by cadmium and tightly binds metal ions. Increased expression levels of MT protein have generally been related to cancer cell survival and resistance to various proapoptotic regimes, including chemotherapy and radiation.…”

mentioning

confidence: 99%

Surface biofunctionalized CdS and ZnS quantum dot nanoconjugates for nanomedicine and oncology: to be or not to be nanotoxic?

Mansur¹,

Mansur²,

Carvalho³

et al. 2016

IJN

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Herein, for the first time, we demonstrated that novel biofunctionalized semiconductor nanomaterials made of Cd-containing fluorescent quantum dot nanoconjugates with the surface capped by an aminopolysaccharide are not biologically safe for clinical applications. Conversely, the ZnS-based nanoconjugates proved to be noncytotoxic, considering all the parameters investigated. The results of in vitro cytotoxicity were remarkably dependent on the chemical composition of quantum dot (CdS or ZnS), the nature of the cell (human cancerous and embryonic types), and the concentration and time period of exposure to these nanomaterials, caused by the effects of Cd 2+ on the complex nanotoxicity pathways involved in cellular uptake. Unexpectedly, no decisive evidence of nanotoxicity of CdS and ZnS conjugates was observed in vivo using intravenous injections in BALB/c mice for 30 days, with minor localized fluorescence detected in liver tissue specimens. Therefore, these results proved that CdS nanoconjugates could pose an excessive threat for clinical applications due to unpredicted and uncorrelated in vitro and in vivo responses caused by highly toxic cadmium ions at biointerfaces. On the contrary, ZnS nanoconjugates proved that the “safe by design” concept used in this research (ie, biocompatible core–shell nanostructures) could benefit a plethora of applications in nanomedicine and oncology.

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“…These compartments harbor proteases, hydrolases, and other enzymes promoting ENM degradation. 92 However, some ENMs (in particular positively charged, basic nanoparticles) are capable of escaping the endosome. This phenomenon has previously been described as the "proton sponge effect".…”

Section: Intracellular Fate and Endosomal Escapementioning

confidence: 99%

Engineered nanomaterial uptake and tissue distribution: from cell to organism

Kettiger¹,

Schipanski²,

Wick³

et al. 2013

IJN

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Exploring Primary Liver Macrophages for Studying Quantum Dot Interactions with Biological Systems

Cited by 74 publications

References 33 publications

Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

Surface biofunctionalized CdS and ZnS quantum dot nanoconjugates for nanomedicine and oncology: to be or not to be nanotoxic?

Engineered nanomaterial uptake and tissue distribution: from cell to organism

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