Protein corona – from molecular adsorption to physiological complexity

• Lennart Treuel,
• Dominic Docter,
• Michael Maskos and
• Roland H. Stauber

Beilstein J. Nanotechnol. 2015, 6, 857–873, doi:10.3762/bjnano.6.88

• composition and the latest findings that help to shed light on temporal evolution of the full serum corona for the first time. Finally, we discuss the most recent advances regarding the molecular-scale mechanistic role of the protein corona in cellular uptake of NPs. Keywords: agglomeration; corona

• charge [4][9] are critical factors determining the formation and nature of the protein corona. The composition and molecular properties of the protein corona have been shown to be influential factors for the cellular uptake of NPs [7][10][11][12] but direct links between structure and effect remain to be

• biological environment. The formation of the biomolecular corona around the NPs modulated their behavior: cells of the blood system seemed to be protected against NP-induced (patho)biological processes by the presence of the corona and also cellular uptake could be promoted [10]. Effect of the corona

Applications of three-dimensional carbon nanotube networks

• Manuela Scarselli,
• Paola Castrucci,
• Francesco De Nicola,
• Ilaria Cacciotti,
• Francesca Nanni,
• Emanuela Gatto,
• Mariano Venanzi and
• Maurizio De Crescenzi

Beilstein J. Nanotechnol. 2015, 6, 792–798, doi:10.3762/bjnano.6.82

• adsorption capacity of the sponge, from the ratio between the final and initial weight after full adsorption [6]. As an example, a CNT-sponge of 2 mg is able to selectively uptake vegetable oil up to 16 times of its initial weight. The observed high value of the uptake efficiency can be ascribed to the

In situ observation of biotite (001) surface dissolution at pH 1 and 9.5 by advanced optical microscopy

• Chiara Cappelli,
• Daniel Lamarca-Irisarri,
• Jordi Camas,
• F. Javier Huertas and
• Alexander E. S. Van Driessche

Beilstein J. Nanotechnol. 2015, 6, 665–673, doi:10.3762/bjnano.6.67

• phlogopite surfaces during dissolution at room temperature. These streaks were described as irregular swelling structures (bulge-type shapes). Their formation was associated with an excess of water uptake influenced by local variations of the TOT-layer charge. Likewise, Aldushin et al. [10] observed bulge

Influence of gold, silver and gold–silver alloy nanoparticles on germ cell function and embryo development

• Ulrike Taylor,
• Daniela Tiedemann,
• Christoph Rehbock,
• Wilfried A. Kues,
• Stephan Barcikowski and
• Detlef Rath

Beilstein J. Nanotechnol. 2015, 6, 651–664, doi:10.3762/bjnano.6.66

• antimicrobial properties [20][21]. This variety in applications generates several potential exposure routes for gold and silver nanoparticles, including injection and inhalation particularly for biomedical applications, but also ingestion and skin contact for medical and consumer products. The uptake behaviour

• amount of particles translocated across the air–blood barrier [22]. The magnitude of particle transfere is inversely correlated to particle size [23]. In contrast, particle uptake following dermal exposure has so far not been observed as nanoparticles do not penetrate beyond the most superficial skin

• layers [24][25]. On the other hand, uptake via ingestion has been proven for silver [26][27][28] as well as gold nanoparticles [29][30]. Interestingly, for AgNP, it has been suggested that mainly ionic silver, released from the actual particles due to dissolution is absorbed via the intestinal tract

Silica micro/nanospheres for theranostics: from bimodal MRI and fluorescent imaging probes to cancer therapy

• Shanka Walia and
• Amitabha Acharya

Beilstein J. Nanotechnol. 2015, 6, 546–558, doi:10.3762/bjnano.6.57

• found that the NPs emitted green light at 510 nm. The magnetic studies suggested that the nanocomposites exhibited typical property of superparamagnetic iron oxide by shortening the relaxation time T2. The cell uptake experiment of these nanocomposites was performed with human mesenchymal stem cells

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

• ). All predilutions were applied 1:10 in serum-free medium to the cells (96er well and transwells: 10 µL NP-dispersion + 90 µL serumfree medium and ibidi wells: 30 µL NP-dispersion + 270 µL serum-free medium). Preliminary, cellular uptake of the NPs was examined for the monocultures of A549 on ibidi µ

• –NH2 at a concentration of 50 µg/mL (58 ± 22% and 59 ± 10%) and 100 µg/mL (49 ± 25% and 29 ± 15%). No cell loss was observed after incubation with aSNP–COOH. Figure 2 shows the cellular uptake of aSNPs with different surfaces in A549 (–plain, –NH2, –COOH; 50 µg/mL). The cells clearly internalized all

• three aSNPs after an incubation time of 4 h in serum-free medium. An approximate quantification of cellular uptake via fluorescence intensity measurement of the images could not be conducted due to the variable fluorescence intensity of the aSNP labeling itself. Comparing all three aSNPs using same

A surface acoustic wave-driven micropump for particle uptake investigation under physiological flow conditions in very small volumes

• Florian G. Strobl,
• Dominik Breyer,
• Phillip Link,
• Adriano A. Torrano,
• Christoph Bräuchle,
• Matthias F. Schneider and
• Achim Wixforth

Beilstein J. Nanotechnol. 2015, 6, 414–419, doi:10.3762/bjnano.6.41

• uptake of nanoparticles. Here, we present a versatile microfluidic device based on acoustic streaming induced by surface acoustic waves (SAWs). The device offers a convenient method for introducing fluid motion in standard cell culture chambers and for mimicking capillary blood flow. We show that shear

• rates over the whole physiological range in sample volumes as small as 200 μL can be achieved. A precise characterization method for the induced flow profile is presented and the influence of flow on the uptake of Pt-decorated CeO2 particles by endothelial cells (HMEC-1) is demonstrated. Under

• physiological flow conditions the particle uptake rates for this system are significantly lower than at low shear conditions. This underlines the vital importance of the fluidic environment for cellular uptake mechanisms. Keywords: acoustic streaming; cellular uptake; flow; nanoparticles; sedimentation; shear

Hematopoietic and mesenchymal stem cells: polymeric nanoparticle uptake and lineage differentiation

• Ivonne Brüstle,
• Thomas Simmet,
• Gerd Ulrich Nienhaus,
• Katharina Landfester and
• Volker Mailänder

Beilstein J. Nanotechnol. 2015, 6, 383–395, doi:10.3762/bjnano.6.38

• cytometry and microscopy analysis showed high uptake rates and no toxicity for all four tested particles in hMSCs and hHSCs. During the differentiation process, the payload of particles per cell decreased. The PLLA–Fe particle showed a significant increase in the IL-8 release in hMSCs but not in hHSCs. We

• into the system, toxicity can occur from the nanoparticles themselves or from the associated components of the nanoparticles that might be released during degradation in vivo. In addition to potentially causing toxicity after cellular uptake, nanoparticles could also alter cellular functions such as

• . The nanoparticles were purified from the surfactant excess by dialysis using Amicon Ultra membrane filters with MWCO 100 kDa (Millipore). The main characteristics of the nanoparticles are described in Table 1. Uptake and toxicity of polymeric nanoparticles Before the nanoparticles were used for

Biological responses to nanoscale particles

• Reinhard Zellner

Beilstein J. Nanotechnol. 2015, 6, 380–382, doi:10.3762/bjnano.6.37

• techniques have been developed to unravel the chemical and molecular mechanistic details, as well as their biological consequences. Depending on whether a given cell spends energy during the uptake of nanoparticles or not, such uptake through the cell membrane is considered to be active or passive. While

• and translocation between cells are important processes which affect not only nanotoxicology but also nano-biomedicine. In the SPP1313, several projects presented experimental strategies to study and dissect nanoparticle uptake. The employed approaches comprised not only technical advancements such as

• novel imaging techniques and particle tracking algorithms, but also generic molecular ways to interfere with uptake mechanisms by using si-RNAs and chemical inhibitors. However, a solid conclusion on whether or not nanoparticle-specific entry routes exist and/or which of the established routes are

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

• nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application. Keywords: cell viability; gold nanoparticles; internalization; Janus particles; quantum dots

• nanoparticles. Recently, it has been shown that macrophages exhibit a higher uptake of rods than spheres [43], whereas in prostate cells the uptake of spheres was more efficient compared to PEGylated rods [44]. Analysis of epithelial cells showed no significant difference in uptake between rods and spheres [45

• and the surface charge of QDs (cationic, anionic, or neutral) on cell metabolism, membrane integrity and uptake, 4) monitored the cellular localization depending on the size and shape of different nanoparticles and finally 5) investigated endocytotic pathways of nanoparticles to gather insights into

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

• dots (QDs) with positively charged cysteamine–QDs, negatively charged dihydrolipoic acid–QDs and zwitterionic D-penicillamine–QDs exposed to canine kidney MDCKII cells. Pretreatment of cells with pharmacological inhibitors suggested that the uptake of nanoparticles was largely due to receptor

• increase the overall size of the nanoparticles, which may alter their uptake mechanism and limit some of their applications. Due to their complex structure and different potential sources of damage (e.g., air and photooxidation, opsonization and enzymatic degradation, mechanical damage, etc.), means for

• and appeared as small but bright fluorescent spots on the membrane and within the cell (Figure 3a). The uptake of single CA–QDs saturated after 11 h, while the number of large CA–QD-aggregates bound to the confluent MDCKII layer evidently increased from 8 to 24 h after addition of the particles

Overview about the localization of nanoparticles in tissue and cellular context by different imaging techniques

• Anja Ostrowski,
• Daniel Nordmeyer,
• Alexander Boreham,
• Cornelia Holzhausen,
• Lars Mundhenk,
• Christina Graf,
• Martina C. Meinke,
• Annika Vogt,
• Sabrina Hadam,
• Jürgen Lademann,
• Eckart Rühl,
• Ulrike Alexiev and
• Achim D. Gruber

Beilstein J. Nanotechnol. 2015, 6, 263–280, doi:10.3762/bjnano.6.25

• . A single technique is often insufficient to address all questions regarding the distribution of NP within the body, the cellular uptake, and the target cells and organs. But a combination of different detection methods may provide reliable information on the NP biodistribution and associated

Release behaviour and toxicity evaluation of levodopa from carboxylated single-walled carbon nanotubes

• Julia M. Tan,
• Jhi Biau Foo,
• Sharida Fakurazi and
• Mohd Zobir Hussein

Beilstein J. Nanotechnol. 2015, 6, 243–253, doi:10.3762/bjnano.6.23

• cellular uptake experiments are required and are currently under investigation. Conclusion In conclusion, a new, versatile nanohybrid based on a very simple method for the administration of LD has been developed. The findings of this study reveal that the loading capacity of SWCNT–COOH is approximately

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

• and specificity in a broad in vitro test is demonstrated. Keywords: biolable; cellular uptake; fluorescence quenching; poylmeric micelles; quantum dots; Introduction One of the main challenges in using high quality nanoparticles for biological applications is to ensure that the ligand system

• . Since cellular uptake mechanisms except from phagocytosis are known to work best with small structures below 150 nm [22], only spherical micelles fulfilling this requirement will be discussed. To ensure a good compatibility between the hydrophobic particles and the inner core of the final micellar

• general (positively or negatively) show a much more efficient adsorption of these proteins needed for the recognition by macrophages [33][34]. Other cell types follow the endocytotic process, which can be receptor mediated or unspecific. For the uptake via endocytosis a positive surface charge has shown

Mechanical properties of MDCK II cells exposed to gold nanorods

• Anna Pietuch,
• Bastian Rouven Brückner,
• David Schneider,
• Marco Tarantola,
• Christina Rosman,
• Carsten Sönnichsen and
• Andreas Janshoff

Beilstein J. Nanotechnol. 2015, 6, 223–231, doi:10.3762/bjnano.6.21

• dark-field microscopy together with transmission electron microscopy to quantify the uptake of gold nanoparticles into MDCK II cells as a function of shape, stabilizing agent, and surface charge [25]. We found that CTAB-coated particles are easily accumulated within cells, while PEG coatings inhibit

• uptake significantly. This is also reflected in the lack of cytotoxicity of PEGylated particles. Interestingly, we also found that spherical particles are more toxic than rod-like ones of the same size and with identical surface functionalization [13]. In contrast to CTAB-coated gold nanorods PEG-coated

• environmental cues also adhesion and uptake of nanoparticles is reflected in the mechanical properties of cells. Figure 3A shows averaged force indentation curves performed on the center of confluent MDCK II cells. Two different models were used to extract mechanical parameters from these data. The first one

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

• underlying uptake mechanisms would be very useful for faster and precise development of nanoparticles for clinical applications. This study aims at the identification of key proteins, which are crucial for the active uptake of iron oxide nanoparticles by HeLa cells (human cervical cancer) as a model cell

• experiments should be carried out with different cell lines and other well-defined nanoparticle species to elucidate possible general principles. Keywords: Caveolin-1; CDC42; endocytosis inhibition; iron oxide nanoparticles; nanoparticle uptake; Introduction Nanotechnology is expected to be a very powerful

• appear in vesicular structures within the cytosol of cells in vitro [19][20][21][22][23][24], which indicates an active, energy dependent uptake via endocytosis. In a post mortem study of glioma patients, who had received thermotherapy with aminosilane coated iron oxide nanoparticles in a phase-II study

Multifunctional layered magnetic composites

• Maria Siglreitmeier,
• Baohu Wu,
• Tina Kollmann,
• Martin Neubauer,
• Gergely Nagy,
• Dietmar Schwahn,
• Vitaliy Pipich,
• Damien Faivre,
• Dirk Zahn,
• Andreas Fery and
• Helmut Cölfen

Beilstein J. Nanotechnol. 2015, 6, 134–148, doi:10.3762/bjnano.6.13

• nacre matrix, the gelatin infiltrated chitin matrix and the magnetic nanocomposite are shown in Figure 8. The swelling degree, Sd, is defined as: where Ws stands for the weight of the swollen sample after swelling equilibrium was reached and Wd stands for the dry weight before water uptake. In the case

• of nacre matrix infiltrated with gelatin a distinct increase in swelling can be observed as compared to the insoluble matrix alone. This effect is not surprising as gelatin alone shows a higher swelling capacity as the insoluble organic matrix. The gravimetric water uptake of the gelatin–chitin

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

• uptake, although the 65Zn-label appeared not to be fully stable. As the degradation of the nanoparticles takes place, the individual transport mechanisms for the different isotopes must be carefully taken into account. Although this variation in transport paths can bring new insights with regard to the

• . In MRI, the correlation of the relaxation times to the local nanoparticle concentrations is difficult due to possible agglomeration, where the increase of hydrodynamic diameters caused by opsonization and the difficulty in the quantification of the degradation and the cellular uptake of particles [22

• term, a 2-compartment model was used for fitting which resulted in a relatively short half-life of 12 d, and very long half-life of ≈1000 d, which cannot be derived precisely from the fit. As a result, the 51Cr label seems adequate for labeling the nanoparticles during blood passage and cell uptake

Synthesis of boron nitride nanotubes and their applications

• Saban Kalay,
• Zehra Yilmaz,
• Ozlem Sen,
• Melis Emanet,
• Emine Kazanc and
• Mustafa Çulha

Beilstein J. Nanotechnol. 2015, 6, 84–102, doi:10.3762/bjnano.6.9

• -employed, aminosilane used in many applications. Ciofani et al. used APTES as an agent for silica coating to functionalize BNNTs [15]. For cellular uptake studies, a fluorescent dye, Oregon Green 488 carboxylic acid, succinimidyl ester was covalently bound to the functionalized BNNTs. The NIH/3T3

• of nanomedicine. The covalent grafting of BNNTs with human transferrin, linked through a carbamide bond, was reported [67]. The transferrin–BNNTs were tested on primary human umbilical vein endothelial cells (HUVECs) to investigate their cellular uptake. It was concluded that the functionalization of

• with GC during a 12 h sonication process. The TEM results indicated that the GC–BNNTs had two different configurations: bamboo-like shaped and noncontinuous walled. HUVECs were treated with the GC–BNNTs and the cellular uptake of the GC–BNNTs was observed. However, the uptake mechanism remains unclear

Materials and characterization techniques for high-temperature polymer electrolyte membrane fuel cells

• Roswitha Zeis

Beilstein J. Nanotechnol. 2015, 6, 68–83, doi:10.3762/bjnano.6.8

• “skin” on the electrode surface. This PTFE-rich layer affects not only the surface conductivity but also the wettability of the catalyst layer. The high PTFE content created a hydrophobic electrode surface, which slowed down the phosphoric acid uptake during the start-up period of the MEA. Mack et al

The fate of a designed protein corona on nanoparticles in vitro and in vivo

• Denise Bargheer,
• Julius Nielsen,
• Gabriella Gébel,
• Markus Heine,
• Sunhild C. Salmen,
• Roland Stauber,
• Horst Weller,
• Joerg Heeren and
• Peter Nielsen

Beilstein J. Nanotechnol. 2015, 6, 36–46, doi:10.3762/bjnano.6.5

• vivo for the respective nanoparticle uptake. Keywords: albumin; 59Fe; 125I; organ uptake; protein corona; SPIOs; transferrin; Introduction Nanoparticles (NPs) have unique capabilities to interact with cells and organs which mark them as attractive working material in nanobioscience and nanomedicine

• a role also in a specific uptake for example in hepatocytes. Discussion Many experimental techniques have been used to investigate the binding of proteins to nanoparticles and some models have been proposed to rationalize the experiments [10][32]. The most accepted view on protein corona formation

• PEGylation, in some highly PEGylated variants (C40K and N10K) obviously no protein was bound. This tunable “postsynthetic” PEGylation of a polymer coated SPIO may offer a way to design a NP which can be optimized for limited macrophage uptake but higher affinity for a target in vivo. Complete suppression of

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

• nanoparticle application from the apical side of the cells [12]. Here, adherent cells are grown to various degrees of confluence, the nanoparticles are applied suspended in cell medium, and finally the uptake and/or the influence on metabolic activity is quantified. Quantification of uptake numbers occurs by

• properties of the coating agent and its reactive group. The impact on surfactant-induced cell behavior was investigated in more detail by interface-sensitive impedance spectroscopy (electric cell–substrate impedance sensing, ECIS). Studies on the uptake and influence on metabolic activity with respect to

• nanoparticles on substrate require in order to prevent their removal by cells seem to be necessary. In previous studies, the cytotoxic impact of apical exposure of the same functionalized nanoparticles to the same epithelial cell line (MDCK II) was presented [18] and the cellular uptake was quantified [20]. It

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

• , Germany Institut für Physik, Universität Augsburg, 86159 Augsburg, Germany Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), 81377 Munich, Germany Department for Mechanical Engineering, Boston University, Boston, MA 02215, USA 10.3762/bjnano.5.256 Abstract The uptake

• of nanoparticles into cells often involves their engulfment by the plasma membrane and a fission of the latter. Understanding the physical mechanisms underlying these uptake processes may be achieved by the investigation of simple model systems that can be compared to theoretical models. Here, we

• present experiments on a massive uptake of silica nanoparticles by giant unilamellar lipid vesicles (GUVs). We find that this uptake process depends on the size of the particles as well as on the thermodynamic state of the lipid membrane. Our findings are discussed in the light of several theoretical

Synthesis and characterization of fluorescence-labelled silica core-shell and noble metal-decorated ceria nanoparticles

• Rudolf Herrmann,
• Markus Rennhak and
• Armin Reller

Beilstein J. Nanotechnol. 2014, 5, 2413–2423, doi:10.3762/bjnano.5.251

• original non-annealed NP were used for biomedical [46] and uptake studies [47], both articles in this issue. What cannot be avoided must be controlled. Since agglomeration is a question of surface properties, it should be possible to control it by surface-active reagents. Consequently, we tried to

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

• 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

• on cell functions. Particles of about 100 nm have previously been shown to be internalized by cells much more efficient than microparticles, which are taken up primarily by phagocytosis, and also more efficient than particles with a size below 100 nm. It was reported that the uptake of 100 nm

• particles was 2.3-fold greater than that of 50 nm particles [44]. Both, macrophages and THP-1 cells rapidly internalized 110 nm PS-COOH and PS-NH2 nanoparticles. However, the amount of internalized nanoparticles, the uptake kinetics, and its mechanism differed between primary cells and the related THP-1