Detection of organic nanoparticles in human bone marrow-derived stromal cells using ToF–SIMS and PCA

Abstract

The detection and localization of polymer-based nanoparticles in human bone marrow-derived stromal cells (hBMSC) by time-of-flight secondary ion mass spectrometry (ToF-SIMS) is reported as an example for the mass spectrometry imaging of organic nanoparticles in cell environments. Polyelectrolyte complex (PEC) nanoparticles (NP) made of polyethylenimine (PEI) and cellulose sulfate (CS), which were developed as potential drug carrier and coatings for implant materials, were chosen for the imaging experiments. To investigate whether the PEI/CS-NP were taken up by the hBMSC ToF-SIMS measurements on cross sections of the cells and depth profiling of whole, single cells were carried out. Since the mass spectra of the PEI/CS nanoparticles are close to the mass spectra of the cells principal component analysis (PCA) was performed to get specific masses of the PEI/CS-NP. Mass fragments originating from the NP compounds especially from cellulose sulfate could be used to unequivocally detect and image the PEI/CS-NP inside the hBMSC. The findings were confirmed by light and transmission electron microscopy. Graphical Abstract During ToF-SIMS analysis Bi3 (+) primary ions hit the sample surface and so called secondary ions (SI) are emitted and detected in the mass analyser. Exemplary mass images of cross sections of human mesenchymal stromal cells (red; m/z = 86.1 u) cultured with organic nanoparticles (green; m/z = 143.0 u) were obtained.

Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation

“…ToF-SIMS has previously been used for studying lipid changes in cells and tissues and is gaining in use because the technique is able to detect a wide range of molecular species with high chemical specificity without the need for labels or probes. 58,59 For instance, ToF-SIMS has been used for studying alterations of lipids in the plasma membrane of macrophage-like THP.1 cells exposed to silver nanoparticles 60 and detecting polymeric nanoparticles in bone-marrow-derived stromal cells, 61 and it can be used for both 2D and 3D imaging of lipid membrane changes in cells. 62,63 The present study applied ToF-SIMS to elucidate the effects of a graphene-based material on cells.…”

Interaction of Poly(l-lysine)/Polysaccharide Complex Nanoparticles with Human Vascular Endothelial Cells

“…Polyelectrolyte complex nanoparticles (PECNP) composed of the polycation poly( l -lysine) (PLL, M W = 50,000 g/mol, (Sigma-Aldrich, Schnelldorf, Germany), in combination with the polyanions cellulose sulfate (CS, degree of substitution d S = 2.8, M W = 1,200,000 g/mol, Janssen, Beerse, Belgium), dextran sulfate (DS, d S = 3.0, M W = 500,000 g/mol, Carl Roth GmbH, Germany) or heparin (HEP, M W = 20,000 g/mol, Carl Roth GmbH, Karlsruhe, Germany) and the fluorescein isothiocyanate (FITC) labeled PECNP species were prepared as described in detail elsewhere [ 11 , 21 , 22 ]. Briefly summarized, 2 mM clear solutions of cationic PLL and anionic CS, DS or HEP were mixed at pH = 7.0 and more or less turbid (milky) dispersions resulted.…”

Visualizing molecular distributions for biomaterials applications with mass spectrometry imaging: a review

“…The ability to track nanoparticles within cells is attracting much interest in the analytical field due in part to the development of nanoparticles capable of delivering therapeutics intracellularly. [85][86][87][88][89][90] SIMS has proven a useful tool for studying such materials and their interactions. 10,87,89,[91][92][93][94][95][96] In a recent study, Hua et al described an innovative microfluidic/sputtering approach allowing SIMS imaging of individual cells in a hydrated environment.…”