From synthetic to natural nanoparticles: monitoring the biodegradation of SPIO (P904) into ferritin by electron microscopy

Abstract

A strong focus on Superparamagnetic Iron Oxide Nanoparticles (SPIOs) has been appreciated recently especially for their use in Magnetic Resonance Imaging (MRI). However, some questions are being raised over these particles due to their long-term toxicity related to the production of toxic free iron during their biodegradation. Here we show by Electron Microscopy how SPIOs (P904) (Guerbet, Paris) are degraded after they are taken up by macrophages, so that iron from the SPIO core is progressively incorporated into the iron-storing protein ferritin (a nontoxic form of iron).

Isoniazid@Fe2O3 Nanocontainers and Their Antibacterial Effect on Tuberculosis Mycobacteria

“…already at INH concentrations as low as 8 mgmL À1 (Figure 4). Similar to the well-established slow and complete dissolution of massive iron oxide nanoparticles under physiological conditions along with concurrent ferretin formation, [17,19] INH is clearly released with advancing nanocontainer dissolution. These specific features of iron oxide-biocompatibility,b iodegradability,s low dissolution [20] -are used in our nanocontainer concept as well.…”

“…Ther esponse of the macrophages was quantified based on reactive oxygen species (ROS), inducible nitric oxide (iNOs), and released lactate dehydrogenase (LDH) (Figure S8,S9). Although substantial ROSf ormation was as expected induced by the Fe-content of the nanoparticles, [17] low levels of NO and LDH indicate as ufficient biocompatibility of the INH@Fe 2 O 3 @DEX nanocontainers. ROSformation in absence of cytotoxic effects,infact, can add another antimicrobial advantage for combating TB as it affects mycobacterial viability,a ctivates cells,a nd immunostimulates cytokine secretion.…”

Isoniazid@Fe2O3‐Nanocontainer mit antibakterieller Wirkung auf Tuberkulose‐Mykobakterien

“…[13] Dabei wurde eine inverse Mikroemulsion mit n-Dodecan als unpolarer Dispersionsphase,Hexadecyltrimethylammoniumbromid (CTAB) als Te nsid, n-Hexanol als Cotensid und verdünntes H 2 . Obwohl aufgrund des Fe-Gehalts der Nanopartikel eine substanzielle ROS-Bildung wie erwartet zu beobachten ist, [17] belegen niedrige Werte für NO und LDH eine ausreichende Bioverträglichkeit der INH@Fe 2 O 3 @-DEX-Nanocontainer.T atsächlich kann die ROS-Bildung in Abwesenheit zytotoxischer Effekte einen zusätzlichen antimikrobiellen Vorteil bei der TB-Abwehr darstellen, da diese sich auf die mykobakterielle Lebensfähigkeit auswirkt, gleichzeitig die Zellen aktiviert und die Zytokin-Sekretion immunostimuliert. [3,18] Um die Aufnahme der Nanocontainer in Makrophagen zu belegen, wurden Zellen auf Kunstoffoberflächen fixiert und "en Face" in parallele Bereiche geschnitten.…”

“…Eine derart hohe Zahl an Nanocontainern in den Makrophagen erlaubt auch den Zugang zu intrazellulären Mykobakterien, die sich nach Phagozytose in den Phagosomen der Makrophagen befinden. [2][3][4][5] [17,19] wird INH offensichtlich mit voranschreitender Auflçsung der Nanocontainer freigesetzt. Diese spezifischen Eigenschaften des EisenoxidsBioverträglichkeit, Bioabbaubarkeit und langsame Auflç-sung [20] -k ommen in unserem Nanocontainer-Konzepts ebenfalls zum Einsatz.…”

Target‑specific delivery of oxaliplatin to HER2‑positive gastric cancer cells in�vivo using oxaliplatin‑au‑fe3o4‑herceptin nanoparticles

“…A number of cationic NPs have been indicated to enter cells by transiently generating holes in the cell membrane (43). However, most of the uptake of NPs into mammalian cells and macrophages usually occurs via endocytosis (44,45). In the present study, TEM indicated that the platinum-tethered NPs synthesized in the present study were internalized by SGC-7901 cells via endocytosis.…”