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

• to enhance the cellular uptake, due to the attractive interaction with the negatively charged cell membrane [35][36]. Therefore, control over the surface chemistry is crucial to study the nanocontainers behavior in vitro and in vivo. Figure 7 shows possible functionalization of PI-b-PEG prior to the

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

• . 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

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

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

• 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

• course, in a biological system, active mechanisms play a key role in cellular uptake. But these examples show that the significance of physical interactions might often be underestimated. This is also indicated in several studies, showing striking similarities between the uptake of membrane-active

• can be internalized independent from complex cell machineries and that lipid domains (rafts) play a crucial role in cellular uptake mechanisms [13][32][53]. An understanding of the unspecific physical aspects of membrane–particle interactions is of vital importance for a discussion of these findings

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

• , positively charged particles were found mostly in leukemia xenografts [43]. With particles left in the cell culture media, the cellular uptake reaches equilibrium within 24 h. When particles were removed from the media, there was virtually an exponential decrease of the amount of particles in proliferating

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

• nanoparticles (NPs) with cells are still not well enough understood. NP size is a key parameter that controls the endocytic mechanism and affects the cellular uptake yield. Therefore, we have systematically analyzed the cellular uptake of fluorescent NPs in the size range of 3.3–100 nm (diameter) by live cells

• as the subcellular distribution upon internalization [21][22][23]. Presently, the effect of NP size on cellular uptake is discussed controversially, which may, at least in part, be associated with the diverse experimental conditions and techniques chosen to monitor NP-cell interactions on cultured

• systematically quantify the uptake kinetics of fluorescent NPs in the size range of 3.3–100 nm (diameter) by live cells. This imaging technique is non-invasive and, because of its high temporal and spatial resolution, well suited to watch NPs invade cells in real time. Here we compare the cellular uptake of NPs

Synthesis of radioactively labelled CdSe/CdS/ZnS quantum dots for in vivo experiments

• Gordon M. Stachowski,
• Christoph Bauer,
• Christian Waurisch,
• Denise Bargheer,
• Peter Nielsen,
• Jörg Heeren,
• Stephen G. Hickey and
• Alexander Eychmüller

Beilstein J. Nanotechnol. 2014, 5, 2383–2387, doi:10.3762/bjnano.5.247

• quantification of the QD concentration during cellular uptake to be calculated. Here, the measured amount of radioactivity can be related to the amount or concentration of the QD ensemble or their metabolites (i.e., ionic species). To avoid any potential chemical inconsistencies we replace the typical precursors

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

• cellular uptake, including optical microscopy, electron microscopy, X-ray microscopy on cells and tissue sections, flow cytometry of isolated skin cells as well as Raman microscopy on whole tissue blocks. In order to assess the biological relevance of such findings, cell viability and free radical

• epidermis is of high relevance. As a result of the special architecture of the skin, levels of interactions include the translocation step across the skin barrier, cellular uptake as well as biological effects. In fact, biological responses to nanoparticle exposure may occur on the cellular level, but also

• were able to isolate skin cells which had taken up particles from treated ex vivo human skin (Figure 1d) [3][11]. In accordance with previous studies, the particle size appeared to be a major determinant for cellular uptake. Notably, after ex vivo topical application of silica particles on human skin

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

• the vast number of toxicological and microbiological studies [7][9][21], only a few studies have investigated whether the differentiation potential of hMSCs was maintained after the uptake of different nanoparticles [31][32][33]. Therefore, the aim of this study was to investigate the cellular uptake

• conclusion, silver nanoparticles with a size of 80 nm (hydrodynamic diameter) were ingested into hMSCs as nanoparticulate material. After cellular uptake, these Ag-NP were mainly associated with the endo-lysosomal cell compartment and occurred as silver agglomerates within these organelles. Exposure of hMSCs

Effects of surface functionalization on the adsorption of human serum albumin onto nanoparticles – a fluorescence correlation spectroscopy study

• Pauline Maffre,
• Stefan Brandholt,
• Karin Nienhaus,
• Li Shang,
• Wolfgang J. Parak and
• G. Ulrich Nienhaus

Beilstein J. Nanotechnol. 2014, 5, 2036–2047, doi:10.3762/bjnano.5.212

• the bare NP surface [2][18][19][20]. To control the biological effects of NPs (e.g., to accomplish targeted delivery to specific cells or tissues or to inhibit cellular uptake), it is extremely important to understand how the properties of the NP surface can control the structure and dynamics of the

Carbon nano-onions (multi-layer fullerenes): chemistry and applications

• Juergen Bartelmess and
• Silvia Giordani

Beilstein J. Nanotechnol. 2014, 5, 1980–1998, doi:10.3762/bjnano.5.207

• (Figure 6). The cytotoxicity and immunomodulatory properties of the synthesized fluorescein-CNO derivative were elucidated and compared with similarly functionalized CNTs. We could show that CNOs exhibit efficient cellular uptake, weak inflammatory potential, and low cytotoxicity and are therefore

• particles have demonstrated high cellular uptake, low cytotoxicity and lower inflammatory potential than CNTs and a very promising future for biomedical applications. HRTEM images of (a) diamond nanoparticles, (b) spherical carbon onions, and (c) polyhedral carbon onions. Diamond nanoparticles are

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

• biological media (i.e., in the presence of proteins) the surface of silver nanoparticles is rapidly coated by a protein corona that influences their physicochemical and biological properties including cellular uptake. Silver nanoparticles are taken up by cell-type specific endocytosis pathways as

• have investigated whether STXM can be applied to investigate the cellular uptake process of silver nanoparticles in human mesenchymal stem cells (hMSC). For this purpose, hMSC were grown on collagen-coated Si3N4-membranes and incubated for 24 h with O2-free aqueous dispersions of silver particles (c

• without major mechanical stress for a cell is a useful tool to detect internalized metallic nanoparticles within cells [86]. As reported in the literature, the cellular uptake of nanoparticles is a conserved process during which extracellular substances are internalized by enclosing them into vesicles

Carbon-based smart nanomaterials in biomedicine and neuroengineering

• Antonina M. Monaco and
• Michele Giugliano

Beilstein J. Nanotechnol. 2014, 5, 1849–1863, doi:10.3762/bjnano.5.196

• were incubated with oxidised NDs, suggesting it was a specific consequence of the surface chemistry of NDs. Nonetheless, Xing and co-workers noted that NDs and oxidised NDs induce overall less DNA damage than that caused by MWCNTs. The investigation of the cellular uptake mechanisms of NDs is also a

• key aspect for biological applications of NDs. Vaijayanthimala and colleagues [75] reported that cellular uptake was strictly related to the surface functionalisation of NDs and that it took place through clathrin-mediated, energy-dependent, endocytosis processes. Schrand et al. [76] also investigated

Biocompatibility of cerium dioxide and silicon dioxide nanoparticles with endothelial cells

• Claudia Strobel,
• Martin Förster and
• Ingrid Hilger

Beilstein J. Nanotechnol. 2014, 5, 1795–1807, doi:10.3762/bjnano.5.190

• indicated a steric stabilization of nanoparticles due to interaction with proteins. After cellular uptake, the CeO2 nanoparticles were localized around the nucleus in a ring-shaped manner. The nanoparticles revealed concentration and time, but no size-dependent effects on the cellular adenosine triphosphate

• predictions are not possible at present. Nevertheless, the different behavior could explained, at least in parts, by the exposure of different intracellular nanoparticle amounts per cell as a result of cell type specific variations in cellular uptake and exocytosis rates. We also investigated the release of

• fibroblasts (BJ cells, American Type Culture Collection (ATCC), USA) were used as positive cells for CD90 (fibroblast phenotype). 10,000 cells were measured for each sample and analysis was performed using CellQuest ProTM software (Becton Dickinson GmbH, Germany). Cellular uptake and intracellular

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

• cellular uptake of the magnetic nanoparticles and enhance their specific targeting effect, surface functionalization has to be employed to coat the nanoparticle surface with ligands that could specifically interact with the receptors overexpressed in the cell membrane. While the size of the dry

Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

• Dagmar A. Kuhn,
• Dimitri Vanhecke,
• Benjamin Michen,
• Fabian Blank,
• Peter Gehr,
• Alke Petri-Fink and
• Barbara Rothen-Rutishauser

Beilstein J. Nanotechnol. 2014, 5, 1625–1636, doi:10.3762/bjnano.5.174

• , Murtenstrasse 50, 3008 Bern, Switzerland Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3000 Bern 9, Switzerland 10.3762/bjnano.5.174 Abstract Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake

• describes two different cellular uptake mechanisms: pinocytosis, which involves the uptake of fluids and molecules within small vesicles and phagocytosis, which is responsible for engulfing large particles (e.g., microorganisms and cell debris). Pinocytosis covers macropinocytosis, clathrin-mediated

• and mβcd-treated A549 cells. The 1 µm particles were not observed inside the epithelial cells under any condition (Figure 5). Discussion For any future biomedical application of engineered NPs, it is mandatory to fundamentally understand their interaction with living systems. The cellular uptake

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

• Adriano A. Torrano Christoph Brauchle Department of Chemistry and Center for NanoScience (CeNS), University of Munich (LMU), Butenandtstrasse 5-13(E), 81377 Munich, Germany 10.3762/bjnano.5.173 Abstract Particle_in_Cell-3D is a powerful method to quantify the cellular uptake of nanoparticles. It

• automatic image analysis. This method is called Particle_in_Cell-3D and was described in detail in a previous publication [5]. In this work we briefly describe Particle_in_Cell-3D and present how it was successfully applied to precisely quantify the cellular uptake of silica and ceria nanoparticles. Silica

• custom-made macro for the widely used ImageJ software [26] and can be downloaded from the ImageJ Documentation Portal [27]. It is a semi-automatic image analysis routine designed to quantify the cellular uptake of nanoparticles by processing image stacks obtained by two-color confocal fluorescence

Current state of laser synthesis of metal and alloy nanoparticles as ligand-free reference materials for nano-toxicological assays

• Christoph Rehbock,
• Jurij Jakobi,
• Lisa Gamrad,
• Selina van der Meer,
• Daniela Tiedemann,
• Ulrike Taylor,
• Wilfried Kues,
• Detlef Rath and
• Stephan Barcikowski

Beilstein J. Nanotechnol. 2014, 5, 1523–1541, doi:10.3762/bjnano.5.165

• approach is centrifugation at varying speed, yielding different size fractions [55]. This method was successfully applied in biological studies dealing with size dependent cellular uptake [56] and bioimaging [57] of gold nanoparticles. However, a rather labour-intensive preparation protocol as well as the

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

• penetration, which need to be considered in in vivo experiments, can be neglected. The kinetics of internalization can depend strongly on the physicochemical properties of the NPs, the type of cells, and other parameters. Cellular uptake studies of NPs require as much characterization of the NP materials as

• cellular uptake [62]. If the cell cultures are turned upside-down, i.e., the cells are hanging in the culture medium, NP agglomerates that have precipitated at the bottom would not reach the cells and thus the effective NP concentration would be dramatically reduced [88]. In contrast, in conventional

• , the eventual loss of internalized NPs as a result of mitotic division, NP exocytosis, or NP transcytosis on the other hand has not been comprehensively studied yet. Cellular uptake studies of NPs require as much characterization of the NP material as currently possible. However, many physicochemical

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

• 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 protein corona protects against size- and dose-dependent toxicity of amorphous silica nanoparticles

• Dominic Docter,
• Christoph Bantz,
• Dana Westmeier,
• Hajo J. Galla,
• Qiangbin Wang,
• James C. Kirkpatrick,
• Peter Nielsen,
• Michael Maskos and
• Roland H. Stauber

Beilstein J. Nanotechnol. 2014, 5, 1380–1392, doi:10.3762/bjnano.5.151

• explanation, corona formation reduced ASP30 cellular uptake, which was however not significantly affected by ASP surface charge in our model. Collectively, our study uncovers an impact of ASP size as well as of the protein corona on cellular toxicity, which might be relevant for processes at the nano–bio

• protein corona on the cellular uptake Nanoparticle uptake is an important determinant for nanopathology [22][34][35]. To investigate the effect of the protein corona on cellular uptake mechanisms we analyzed the uptake of two fluorescently labeled ASPs with comparable physico-chemical characteristics

• carboxylation (ASP30F versus ASP30-COOH; Table 1) we did not, however, observe a significant difference in cellular uptake (Figure 7A/B). As reflected by the rather similar zeta potential after incubation of the different ASP in protein-containing medium the protein corona seems to shield the charged ASP

Antimicrobial properties of CuO nanorods and multi-armed nanoparticles against B. anthracis vegetative cells and endospores

• Pratibha Pandey,
• Merwyn S. Packiyaraj,
• Himangini Nigam,
• Gauri S. Agarwal,
• Beer Singh and
• Manoj K. Patra

Beilstein J. Nanotechnol. 2014, 5, 789–800, doi:10.3762/bjnano.5.91

• particles were spear shaped with one tapered end. Most likely the tapered spears of P5 penetrate easily into the bacterial cell on collision causing more cellular damage and cell death compared to the nanorods. The shape of the nanoparticles is known to be an important contributor in their cellular uptake