Pulmonary surfactant augments cytotoxicity of silica nanoparticles: Studies on an in vitro air–blood barrier model

• Jennifer Y. Kasper,
• Lisa Feiden,
• Maria I. Hermanns,
• Christoph Bantz,
• Michael Maskos,
• Ronald E. Unger and
• C. James Kirkpatrick

Beilstein J. Nanotechnol. 2015, 6, 517–528, doi:10.3762/bjnano.6.54

• extracellular ROS production or could trigger a cellular ROS production following internalization of the aSNPs. Extracellular ROS production likewise causes membranolysis [33][37][39][40]. To verify this hypothesis aSNP-stimulated A549 with and without Alveofact® was checked for ROS over a period of 20 min to

Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

• Lisa Landgraf,
• Ines Müller,
• Peter Ernst,
• Miriam Schäfer,
• Christina Rosman,
• Isabel Schick,
• Oskar Köhler,
• Hartmut Oehring,
• Vladimir V. Breus,
• Thomas Basché,
• Carsten Sönnichsen,
• Wolfgang Tremel and
• Ingrid Hilger

Beilstein J. Nanotechnol. 2015, 6, 300–312, doi:10.3762/bjnano.6.28

• field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a

• endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized

• by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of

The effect of surface charge on nonspecific uptake and cytotoxicity of CdSe/ZnS core/shell quantum dots

• Vladimir V. Breus,
• Anna Pietuch,
• Marco Tarantola,
• Thomas Basché and
• Andreas Janshoff

Beilstein J. Nanotechnol. 2015, 6, 281–292, doi:10.3762/bjnano.6.26

• cell (in this time regime). In order to estimate the extent of QD internalization within MDCKII cells upon exposure, and to investigate the kinetics of their nonspecific interaction, a series of fluorescence images of different areas of MDCKII confluent layers was acquired during 24 hours of exposure

• interior during the first 6 h after addition of QDs. For longer exposure times, the cell interior close to the nucleus displays more particles (Figure 3c). In order to elucidate the mechanism of QD internalization by MDCKII cells, we studied nonspecific interactions between QDs and inhibitor-treated MDCK

Tailoring the ligand shell for the control of cellular uptake and optical properties of nanocrystals

• Johannes Ostermann,
• Christian Schmidtke,
• Christopher Wolter,
• Jan-Philip Merkl,
• Hauke Kloust and
• Horst Weller

Beilstein J. Nanotechnol. 2015, 6, 232–242, doi:10.3762/bjnano.6.22

• unspecific interactions with cells, like macrophages, epithelic or endothelic cells [32]. For macrophages the internalization process follows the typical steps of phagocytosis, which is controlled by the adsorption of specific proteins on the surface of the nanocontainer. Hydrophobic and charged particles in

Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

• Nils Bohmer and
• Andreas Jordan

Beilstein J. Nanotechnol. 2015, 6, 167–176, doi:10.3762/bjnano.6.16

• development of new therapies for numerous diseases. For example iron oxide nanoparticles are in clinical use already in the thermotherapy of brain cancer. Although it has been shown, that tumor cells take up these particles in vitro, little is known about the internalization routes. Understanding of the

• on the surface characteristics of the nanoparticles and the experimental design. Knockdown of CDC42 showed a 46% decrease of the internalization of PEGylated SPIONs within 24 h incubation time. Knockdown of Dynamin 2, Flotillin-1, Clathrin and PIP5Kα caused no or only minor effects. Hence endocytosis

• of the SCIONs was chosen after preliminary experiments. It could be shown that 5 µg Fe/mL provides the lowest background fluorescence combined with a good intracellular signal. In both setups the cell culture media contains SCIONs in excess to the internalization rate of the cells. Afterward cells

The distribution and degradation of radiolabeled superparamagnetic iron oxide nanoparticles and quantum dots in mice

• Denise Bargheer,
• Artur Giemsa,
• Barbara Freund,
• Markus Heine,
• Christian Waurisch,
• Gordon M. Stachowski,
• Stephen G. Hickey,
• Alexander Eychmüller,
• Jörg Heeren and
• Peter Nielsen

Beilstein J. Nanotechnol. 2015, 6, 111–123, doi:10.3762/bjnano.6.11

• cellular internalization and processing of polymer-coated Qdots and SPIOs was gained by cell culture. For comparison of the in vivo data, these studies were made with J774 cells (a murine macrophage cell line). The cells were incubated with polymer-coated Qdots for 2 h, then the nanoparticles were removed

Mammalian cell growth on gold nanoparticle-decorated substrates is influenced by the nanoparticle coating

• Christina Rosman,
• Sebastien Pierrat,
• Marco Tarantola,
• David Schneider,
• Eva Sunnick,
• Andreas Janshoff and
• Carsten Sönnichsen

Beilstein J. Nanotechnol. 2014, 5, 2479–2488, doi:10.3762/bjnano.5.257

• cell migration and no significant particle internalization occurred. Concerning cell adhesion and spreading as compared to cell growth on bare substrates after 3 days of incubation, a reduction by 45% and 95%, respectively, for the surfactant particle coating was observed, whereas the amino-terminated

• special functionality), this study is focused on the impact of basolateral exposure of gold nanoparticles on epithelial cells. Here, epithelial cells were exposed to nanoparticles adsorbed onto a surface. Since MDCK II cells exhibit caveolae only basolaterally, it is conceivable that internalization is

• nanoparticle surface, and direct chemical binding are possible candidates. For an internalization of particles into the cell, the contact strength between the particle and the membrane must overcome the van der Waals forces, keeping the particles immobilized on the substrate. In regions where the cell membrane

Intake of silica nanoparticles by giant lipid vesicles: influence of particle size and thermodynamic membrane state

• Florian G. Strobl,
• Florian Seitz,
• Christoph Westerhausen,
• Armin Reller,
• Adriano A. Torrano,
• Christoph Bräuchle,
• Achim Wixforth and
• Matthias F. Schneider

Beilstein J. Nanotechnol. 2014, 5, 2468–2478, doi:10.3762/bjnano.5.256

• massive particle uptake takes place. Figure 3 illustrates this situation. During the uptake process, the vesicle radius, i.e., the membrane area shrinks continuously, whereas the intravesicular particle concentration increases. Furthermore, the particles become visible after internalization in the optical

• internalization of particle agglomerates. Taken together, further experiments will be necessary to exclude these mentioned effects. The relevance of the membrane bending stiffness for the observed phenomena still remains questionable. Especially for the large 123 nm particles, it will probably play a minor role

• the typical relaxation time of membrane defects. Both parameters are very important for uptake processes. The facts, that massive internalization of particles can be driven by unspecific interaction of lipid membranes and that this is dependent on the phase state of the membrane are highly relevant

Functionalized polystyrene nanoparticles as a platform for studying bio–nano interactions

• Cornelia Loos,
• Tatiana Syrovets,
• Anna Musyanovych,
• Volker Mailänder,
• Katharina Landfester,
• G. Ulrich Nienhaus and
• Thomas Simmet

Beilstein J. Nanotechnol. 2014, 5, 2403–2412, doi:10.3762/bjnano.5.250

• recognition and internalization of particulate matter including nanoparticles. As a consequence, macrophages accumulate with time a main portion of nanoparticles incorporated by the body [25]. Thus, the clinically approved superparamagnetic iron oxide (SPIO) MRI contrast agent ResovistTM is taken up after

• implicated in the development of atherosclerosis [27]. In vitro studies showed that this receptor is engaged in the internalization of negatively charged ResovistTM, a SPIO of 20–60 nm in size, by human macrophages via clathrin-mediated endocytosis. Hence, the uptake of negatively charged nanoparticles of

• of specific receptors engaged in the uptake might dictate the rate of particle internalization by a cell. We have shown that in the presence of serum, macrophages take up nanoparticles by phagocytosis using specific interaction with an antibody receptor CD64, which is specifically expressed on the

Nanoparticle interactions with live cells: Quantitative fluorescence microscopy of nanoparticle size effects

• Li Shang,
• Karin Nienhaus,
• Xiue Jiang,
• Linxiao Yang,
• Katharina Landfester,
• Volker Mailänder,
• Thomas Simmet and
• G. Ulrich Nienhaus

Beilstein J. Nanotechnol. 2014, 5, 2388–2397, doi:10.3762/bjnano.5.248

• . By using spinning disk confocal microscopy in combination with quantitative image analysis, we studied the time courses of NP association with the cell membrane and subsequent internalization. NPs with diameters of less than 10 nm were observed to accumulate at the plasma membrane before being

• machinery in order to trigger the subsequent internalization. Keywords: cell membrane; endocytosis; fluorescence microscopy; nanoparticle; size effect; Introduction Understanding the interaction between engineered nanomaterials and living matter has attracted increasing attention in recent years

• it determines the biological identity of the NP. The key role of a cellular membrane is to provide a strict separation between the cytosol and the extracellular environment, and to selectively control the flow of ions and molecules into and out of the cell. For internalization of larger chunks of

Interaction of dermatologically relevant nanoparticles with skin cells and skin

• Annika Vogt,
• Fiorenza Rancan,
• Sebastian Ahlberg,
• Berouz Nazemi,
• Chun Sik Choe,
• Maxim E. Darvin,
• Sabrina Hadam,
• Ulrike Blume-Peytavi,
• Kateryna Loza,
• Jörg Diendorf,
• Matthias Epple,
• Christina Graf,
• Eckart Rühl,
• Martina C. Meinke and
• Jürgen Lademann

Beilstein J. Nanotechnol. 2014, 5, 2363–2373, doi:10.3762/bjnano.5.245

• and subsequent isolation of keratinocytes and Langerhans cells, only the internalization of 42 nm, but not of 75 or 200 nm particles could be identified. Interestingly, the size limit for penetration and cellular uptake appears to differ among different particle types. In previous studies of our

• groups, we observed penetration and cellular uptake of fluorescent polystyrene particles ranging from 40–200 nm in diameter after skin surface stripping in murine and human skin [11][12]. Furthermore, the internalization of a fluorescent vaccinia virus vector (diameter approx. 290 nm) could be

• tissue raises the question whether nanomaterials ever have the chance to translocate the skin barrier on the single-particle level, or how the adsorption of skin surface material and secondary changes in particle properties will affect penetration and internalization by cells. Also, results obtained from

Anticancer efficacy of a supramolecular complex of a 2-diethylaminoethyl–dextran–MMA graft copolymer and paclitaxel used as an artificial enzyme

• Yasuhiko Onishi,
• Yuki Eshita,
• Rui-Cheng Ji,
• Masayasu Onishi,
• Takashi Kobayashi,
• Masaaki Mizuno,
• Jun Yoshida and
• Naoji Kubota

Beilstein J. Nanotechnol. 2014, 5, 2293–2307, doi:10.3762/bjnano.5.238

• the modulation of the AP-GA-triggered stress responses in cells because of the differences in the internalization mechanism, subcellular localization, and concentration gradients in cells [5][6]. Above all, the DDS complex must be not degraded in cells and act as an intact object. Nishiyama et al. [7

Effect of silver nanoparticles on human mesenchymal stem cell differentiation

• Christina Sengstock,
• Jörg Diendorf,
• Matthias Epple,
• Thomas A. Schildhauer and
• Manfred Köller

Beilstein J. Nanotechnol. 2014, 5, 2058–2069, doi:10.3762/bjnano.5.214

• of silver under these experimental conditions. In summary, the internalization of nano-silver into stem cells had a significant influence on diverse aspects of cellular functions. Therefore, more studies are needed to investigate the effects of nano-silver in directing stem cell behavior in order to

PVP-coated, negatively charged silver nanoparticles: A multi-center study of their physicochemical characteristics, cell culture and in vivo experiments

• Sebastian Ahlberg,
• Alexandra Antonopulos,
• Jörg Diendorf,
• Ralf Dringen,
• Matthias Epple,
• Rebekka Flöck,
• Wolfgang Goedecke,
• Christina Graf,
• Nadine Haberl,
• Jens Helmlinger,
• Fabian Herzog,
• Frederike Heuer,
• Stephanie Hirn,
• Christian Johannes,
• Stefanie Kittler,
• Manfred Köller,
• Katrin Korn,
• Wolfgang G. Kreyling,
• Fritz Krombach,
• Jürgen Lademann,
• Kateryna Loza,
• Eva M. Luther,
• Marcelina Malissek,
• Martina C. Meinke,
• Daniel Nordmeyer,
• Anne Pailliart,
• Jörg Raabe,
• Fiorenza Rancan,
• Barbara Rothen-Rutishauser,
• Eckart Rühl,
• Carsten Schleh,
• Andreas Seibel,
• Christina Sengstock,
• Lennart Treuel,
• Annika Vogt,
• Katrin Weber and
• Reinhard Zellner

Beilstein J. Nanotechnol. 2014, 5, 1944–1965, doi:10.3762/bjnano.5.205

• internalization of silver nanoparticles in astrocytes as in the cell types discussed above (Figure 11), inhibitors of macropinocytosis and endosomal trafficking (chloroquine and amiloride) at least partially lower the accumulation of silver nanoparticles [108]. Accumulated silver nanoparticles appear to be quite

Influence of surface-modified maghemite nanoparticles on in vitro survival of human stem cells

• Michal Babič,
• Daniel Horák,
• Lyubov L. Lukash,
• Tetiana A. Ruban,
• Yurii N. Kolomiets,
• Svitlana P. Shpylova and
• Oksana A. Grypych

Beilstein J. Nanotechnol. 2014, 5, 1732–1737, doi:10.3762/bjnano.5.183

• biological application of foreign objects, the surface of the nanoparticles has to be coated by a biocompatible shell to prevent undesirable interactions of particles with the environment and to enable their internalization by the cells. At the same time coating avoids particle aggregation. Last but not

• least, the surface shell of the magnetic cores has to participate actively in the uptake of the conjugates, proteins and/or antibodies. Internalization (transfection) agents [10] or specific targeting groups [11][12] are therefore often bound to the particles in order to support their uptake by the

Precise quantification of silica and ceria nanoparticle uptake revealed by 3D fluorescence microscopy

• Adriano A. Torrano and
• Christoph Bräuchle

Beilstein J. Nanotechnol. 2014, 5, 1616–1624, doi:10.3762/bjnano.5.173

• medical treatment, and also for a correct risk assessment of nanoparticles. In both cases, knowledge regarding the kinetics of particle internalization gives the dose as a function of the time and allows for the investigation of a variety of parameters on that might influence the uptake behavior. Typical

• nanoparticles, possibly influenced by cell division. Particle_in_ell-3D can be applied to investigate the dose-dependent effects for the risk assessment of nanoparticles. Additionally, this method can be used to study which factors are determinant for the successful attachment, internalization and cargo release

In vitro interaction of colloidal nanoparticles with mammalian cells: What have we learned thus far?

• Moritz Nazarenus,
• Qian Zhang,
• Mahmoud G. Soliman,
• Pablo del Pino,
• Beatriz Pelaz,
• Susana Carregal-Romero,
• Joanna Rejman,
• Barbara Rothen-Rutishauser,
• Martin J. D. Clift,
• Reinhard Zellner,
• G. Ulrich Nienhaus,
• James B. Delehanty,
• Igor L. Medintz and
• Wolfgang J. Parak

Beilstein J. Nanotechnol. 2014, 5, 1477–1490, doi:10.3762/bjnano.5.161

• ., "yes" or "no"), but rather are based on different kinetics. However, non-adhesive cell lines, i.e., cell suspensions, can be different and examples in which no significant internalization of NPs happened are reported [31]. Coming back to adhesive cell-lines, the first step in NP internalization

• parameters are typically asked over the time course required for NP internalization and subcellular localization, and are not tracked over long time courses. It is generally accepted that NPs are partitioned during cell division, in which they are passed to the daughter cells [76][77]. Such dilution effect

• internalization? As mentioned before, virtually all NPs are spontaneously internalized by adherent cells, mainly cell lines, that are usually grown on a certain support and covered with cell culture medium under static conditions. In this case, NPs in the medium can directly access cells, and issues like tissue

Protein-coated pH-responsive gold nanoparticles: Microwave-assisted synthesis and surface charge-dependent anticancer activity

• Dickson Joseph,
• Nisha Tyagi,
• Christian Geckeler and
• Kurt E.Geckeler

Beilstein J. Nanotechnol. 2014, 5, 1452–1462, doi:10.3762/bjnano.5.158

• by different proteins at fixed concentrations is speculated to be due to the degree of internalization of the AuNPs into the cells, which is supported here by the zeta potential studies. The internalization of AuNPs highly depends upon the surface charge of the AuNPs. Thus, the surface charges on the

• acidic pH (which is considered to be the pH in cancer cells) [60] was positive and negative at pH 7 (Figure 5). Hence higher cell internalization takes place in an acidic environment causing greater toxicity compared to neutral pH. The IC50 values of the different protein-coated AuNPs followed the order

• differential effect of AuNPs on the cell viabilities of the fibroblasts and the cancer cell lines. Additional studies, such as cellular uptake and in vivo studies must be conducted to unravel the mechanism involved in the internalization of AuNPs and to understand the anticancer properties of the prepared

The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver

• Markus Heine,
• Alexander Bartelt,
• Oliver T. Bruns,
• Denise Bargheer,
• Artur Giemsa,
• Barbara Freund,
• Ludger Scheja,
• Christian Waurisch,
• Alexander Eychmüller,
• Rudolph Reimer,
• Horst Weller,
• Peter Nielsen and
• Joerg Heeren

Beilstein J. Nanotechnol. 2014, 5, 1432–1440, doi:10.3762/bjnano.5.155

• that after their internalization nanocrystals are not degraded within 30 min. The storage of oleic acid-coated nanocrystals within these lipophilic, intracellular compartments probably inhibits the release of free iron ions thereby preventing the generation of reactive oxygen species and inflammatory

• intracellular multiprotein oligomer, the so-called-inflammasome [31], which can be activated by intracellular aggregates such as ureate or cholesterol crystals [32]. Notably, hepatic internalization of Ferinject® or SPIOs delivered by polymer or lipid micelles did not influence Il1b gene expression underlining

• ] and therefore it is implausible that this cell type is quantitatively important for lipid micelles internalization. Nevertheless, these specialized macrophages bearing high phagocytic activity are part of the innate immune system [25] and their stimulation can activate the transcription of pro

Nanodiamond-DGEA peptide conjugates for enhanced delivery of doxorubicin to prostate cancer

• Amanee D Salaam,
• Patrick Hwang,
• Roberus McIntosh,
• Hadiyah N Green,
• Ho-Wook Jun and
• Derrick Dean

Beilstein J. Nanotechnol. 2014, 5, 937–945, doi:10.3762/bjnano.5.107

• drug concentrations, DOX efficacy was enhanced. The quantitative analysis of DOX release kinetics and cellular internalization are limitations of this study and should be the subject of future studies. Conclusion In this study, a novel targeted drug delivery system consisting of NDs (drug delivery

Injection of ligand-free gold and silver nanoparticles into murine embryos does not impact pre-implantation development

• Ulrike Taylor,
• Wiebke Garrels,
• Annette Barchanski,
• Svea Peterson,
• Laszlo Sajti,
• Andrea Lucas-Hahn,
• Lisa Gamrad,
• Ulrich Baulain,
• Sabine Klein,
• Wilfried A. Kues,
• Stephan Barcikowski and
• Detlef Rath

Beilstein J. Nanotechnol. 2014, 5, 677–688, doi:10.3762/bjnano.5.80

• embryo [14]. However, spontaneous uptake can result into a very heterogeneous nanoparticle load among cells [51] while electroporation of embryos for nanoparticle internalization has not been attempted yet. Therefore, even if the injection of nanoparticles does not actually mirror nanoparticle exposure

Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats

• Nadine Haberl,
• Stephanie Hirn,
• Alexander Wenk,
• Jörg Diendorf,
• Matthias Epple,
• Blair D. Johnston,
• Fritz Krombach,
• Wolfgang G. Kreyling and
• Carsten Schleh

Beilstein J. Nanotechnol. 2013, 4, 933–940, doi:10.3762/bjnano.4.105

• uptake of particles into the cells and a subsequent release of the proinflammatory cytokines IL-6 and IL-8 [30][31]. Moreover, Greulich et al. described the internalization of AgNP to be a clathrin-mediated process [31]. The clathrin-mediated process of internalization after incubation of human

Paper modified with ZnO nanorods – antimicrobial studies

• Mayuree Jaisai,
• Sunandan Baruah and
• Joydeep Dutta

Beilstein J. Nanotechnol. 2012, 3, 684–691, doi:10.3762/bjnano.3.78

• in cellular internalization of ZnO nanoparticles has also been observed by Appierot et al. [6] in a study of their antibacterial effect on E. coli and S. aureus. This work reports on an antimicrobial paper containing zinc oxide (ZnO) nanorods grown by a hydrothermal process, and which can be used for