The Fate of SWCNTs in Mouse Peritoneal Macrophages: Exocytosis, Biodegradation, and Sustainable Retention

Abstract

The understanding of toxicological and pharmacological profiles of nanomaterials is an important step for the development and clinical application of nanomedicines. Carbon nanotubes (CNTs) have been extensively explored as a nanomedicine agent in pharmaceutical/biomedical applications, such as drug delivery, bioimaging, and tissue engineering. The biological durability of CNTs could affect the function of CNTsbased nanomedicines as well as their toxicity in cells and tissues. Therefore, it is crucial to assess the fate of nanomedicine in phagocytes. Herein, we investigated the candidate fate of acid-oxidized single-walled carbon nanotubes (SWNCTs) in nonactivated primary mouse peritoneal macrophages (PMQ). The sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results showed that the intracellular SWCNTs continued growing from 4 to 36 h in PMQ. After replacing the exposure medium, we found the exosome induced by SWCNTs on the surface of macrophages according to scanning electron microscope (SEM) observation. The near-infrared (NIR) absorption increase of the supernatant samples after post-exposure indicates that SWCNTs exocytosis occurred in PMQ. The decreasing intracellular SWCNTs amount suggested the incomplete biodegradation in PMQ, which was confirmed by Raman spectroscopy and transmission electron microscopy (TEM). The combined data reveal that SWCNTs could be retained for more than 60 h in macrophages. Then sustainable retention of SWCNTs in primary macrophages was coexist with exocytosis and biodegradation. The findings of this work will shed light on the bioimaging, diagnosis and other biomedical applications of CNTs-based nanomedicines.

Single-Walled Carbon Nanotubes Attenuate Cytotoxic and Oxidative Stress Response of Pb in Human Lung Epithelial (A549) Cells

“…Understanding the fate and retention time of SWCNTs in cells and living organisms are important points for biomedical application of SWCNTs [63]. Welsher et al [64] reported that SWCNTs were distributed throughout the body after intravenous injection to mice.…”

Nanomaterial Exposure, Extracellular Vesicle Biogenesis and Adverse Cellular Outcomes: A Scoping Review

“…Thirteen articles performed in vitro studies; in vivo studies were used in two articles, two studies performed hybrid assays (in vitro and in vivo), and only one article performed a clinical trial exploring patient-derived EVs. It is important to note that only two studies performed tests that referred to the quality control of the biological sample, namely cell viability and authenticity [ 26 , 39 ]. Medical tests were used in the clinical-trial study to select the sample group and exclude confounding variables such as blood characteristics that could promote changes in the collected biological sample [ 24 ].…”

“…[ 24 , 40 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. The remaining studies used nanotubes, nanoclusters, nanosheets, as well as dendrimers [ 26 , 49 , 50 , 51 ]. As for the characteristics of NMs, only six of the studies analyzed and reported the zeta potential, two reported the polydispersity index, four analyzed the presence of contaminants (e.g., endotoxins as relevant for immune effects), and three reported the purity as quality control of the NMs.…”

“…Only eight studies reported analysis regarding EV size, with studies referring to ‘exosome’ isolation reporting mean diameters ranging from 30–200 nm while EVs generally range from 60–1000 nm. Compared with the control, six studies reported no significant differences in EV size in response to NM exposure [ 26 , 39 , 41 , 45 , 49 , 51 ], while one study observed a decrease in EV size [ 46 ], and one study reported an increase in EV size [ 25 ]. Interestingly, the impact of NMs on EV biogenesis is evident.…”

“…Emerging evidence suggests that the NM exposure of cells and organs stimulates the secretion and disturbs EV biogenesis by activating various biological processes that include immune-system activation, toxicity reduction mediated by exocytosis of NMs through EVs, and the induction of pro-thrombotic effects in cardiovascular and metabolic diseases [ 20 , 21 , 22 , 23 , 24 , 25 ]. Interestingly, EVs have demonstrated the importance of explaining the possible outcomes of many physiological processes, including the cytotoxic and inflammatory processes induced by NMs [ 10 , 20 , 26 ]. With the vast diversity of NMs that humans are widely exposed to, significant roles for EVs in the context of NM toxicology and hence diverse physiological and pathological outcomes can be expected.…”