Effects of iron oxide nanoparticles on biological responses and MR imaging properties in human mammary healthy and breast cancer epithelial cells

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs, diameters >50 nm) have received great attention due to their promising use as magnetic resonance imaging (MRI) contrast agents. In this study, we evaluated the cellular uptake and biological responses in vitro of ultrasmall SPIONs (USPIONs, diameters < 50 nm). We compared the cellular responses between breast epithelia isolated from healthy and breast cancer donors after exposure to carboxy-terminated USPIONs (10 and 30 nm PEG-coated, 10 and 30 nm non-PEG-coated). The particles were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS) and gel electrophoresis. Cellular interactions with USPIONs were assessed by confocal microscopy and TEM. Cellular uptake of USPIONs was quantified using ICP-MS. Cell viability was measured by MTT and neutral red uptake assays. T2* weighted MRI scans were performed using a 7T scanner. Results demonstrated that cell association/internalization of USPIONs was size- and surface coating-dependent (PEG vs. non-PEG), and higher cellular uptake of 10 and 30 nm non-coated particles was observed in both cell types compared with PEG-coated particles. Cell uptake for 10 and 30 nm non-coated particles was higher in cancer cells from two of three tested donors compared to healthy cells from three donors. There was no significant cytotoxicity observed for all tested particles. Significantly enhanced MRI contrast was observed following exposure to 10 and 30 nm non-coated particles compared to PEG-coated particles in both cell types. In comparison, cancer cells showed more enhanced MRI signals when compared to normal cells. The data indicate that cell responses following exposure to USPIONs are dependent on particle properties. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1032-1042, 2016.

Biomimetic Magnetoliposomes as Oxaliplatin Nanocarriers: In Vitro Study for Potential Application in Colon Cancer

“…A reduction in the IC 50 of free OXA is observed in most tumor cell lines when treated with pegylated nanoformulations, being especially remarkable such reduction in HT29. The reduction of the IC 50 with the new nanoformulations (Oxa-BMLs and Oxa-BMLs-PEG) is not as pronounced as it was with the Oxa-BMNPs nanoassemblies of previous works described by Jabalera et al [14], which is probably due to the lower internalization of the former, as previously described above and in accordance with results from other authors [57,58]. Results from this study represent a true stepforward in this research area, since it is the first study in which nanoformulations are designed to locally release Oxa in which both a reduction of the IC 50 compared to that for free Oxa, and an improvement of their biocompatibility and cellular uptake have been demonstrated.…”

Cytotoxicity, cellular uptake and apoptotic responses in human coronary artery endothelial cells exposed to ultrasmall superparamagnetic iron oxide nanoparticles

“…Both assays were employed to get more conclusive information related to nanoparticle cytotoxicity using two different orthogonal methods. For the Alamar Blue assay, background interference caused by USPION was corrected by subtracting the fluorescence values from particles in cell‐free media from the final absorbance value for each treatment (Coccini, Grandi, Lonati, Locatelli, & De Simone, ; Zhang et al, ). A concentration‐dependent decrease in cell viability was observed with the Alamar Blue assay, with means 81%, 72%, 56% and 53% of control after exposure to 25, 50, 100 and 200 μg/mL USPION, respectively (Figure A).…”

“…The physicochemical properties of USPION make them excellent candidates for biomedical applications (Bashir, Bhatti, Marin, & Nelson, ; Bhattarai et al, ; Bobo, Robinson, Islam, Thurecht, & Corrie, ; Cicha et al, ; Matuszak et al, ; Zaloga et al, ; Zhang et al, ). Current medical uses include magnetic resonance image (MRI) contrast agents, lymph node localization devices, targeted drug delivery systems and cancer theranostic applications (Lee et al, ; Zhang et al, ). USPION have also been approved or cleared by the US Food and Drug Administration for drug and medical device applications (Douek et al, ; Dulinska‐Litewka et al, ; Thakor et al, ; Thill et al, ).…”

Microwave-Assisted Synthesis of SPION-Reduced Graphene Oxide Hybrids for Magnetic Resonance Imaging (MRI)

“…T 1 contrast agents are composed of paramagnetic metal ions, which have a permanent magnetic moment due to unpaired electrons that stimulate the energy transfer from nuclear spins to environment, thus reducing T 1 relaxation. The mechanism of preferential T 2 /T 2 * shortening by the so-called T 2 contrast agents is derived from bulk susceptibility effects and distortions of the local magnetic field [2,3,4,5,6,7,8]. Different studies have been reported on the development of contrast agents based on inorganic nanoparticles [9,10,11,12,13].…”