Nanoparticle delivery to metastatic breast cancer cells by nanoengineered mesenchymal stem cells

• Liga Saulite,
• Karlis Pleiko,
• Ineta Popena,
• Dominyka Dapkute,
• Ricardas Rotomskis and
• Una Riekstina

Beilstein J. Nanotechnol. 2018, 9, 321–332, doi:10.3762/bjnano.9.32

• , Vilnius University, Sauletekio Ave. 7, LT-10257 Vilnius, Lithuania, Laser Research Centre, Vilnius University, Sauletekio al. 9, corp. 3, LT-10222 Vilnius, Lithuania 10.3762/bjnano.9.32 Abstract We created a 3D cell co-culture model by combining nanoengineered mesenchymal stem cells (MSCs) with the

• ; mesenchymal stem cells; quantum dots; spheroids; 3D cell culture; Introduction The recent progress in the development of nanoscale agents opens up new perspectives for targeted drug delivery in cancer diagnostics, imaging and therapy. However, once administered into the body, nanoparticles (NPs) are rapidly

• and their immune privileged nature, mesenchymal stem cells (MSCs) can be used as a delivery vehicle for therapeutic and imaging agents, such as drug-conjugated NPs [3][4]. MSCs are adult stem cells that can be isolated from various organs, including brain, liver, kidney, lung, bone marrow, muscle

Liquid-crystalline nanoarchitectures for tissue engineering

• Baeckkyoung Sung and
• Min-Ho Kim

Beilstein J. Nanotechnol. 2018, 9, 205–215, doi:10.3762/bjnano.9.22

• ) [40]. Locally ordered collagen type-I gels, obtained by solvent evaporation, could induce an aligned 2D growth of human mesenchymal stem cells as well as their guided differentiation into bone tissues within two weeks in osteogenic media [86]. The concentrated (ca. 90 mg/mL) collagen type-I film

• stem cells [7][98]. Investigations by the Hegmann group have shown that bioengineered LCE scaffolds can be used to control mechanical response, growth direction, and proliferation rate of the seeded myoblasts and neuroblastomers. Porous LCE matrices in smectic-A with interdigitated cholesterol moieties

• local alignments, which resulted in directed and oriented growth of human mesenchymal stem cells and their osteogenic differentiation [105]. Additionally, biomineralization-mimicking hybrid materials, using chitin nanowhisker gel matrices in a nematic phase as templates for CaCO3 crystallization, have

Synthesis and functionalization of NaGdF₄:Yb,Er@NaGdF₄ core–shell nanoparticles for possible application as multimodal contrast agents

• Dovile Baziulyte-Paulaviciene,
• Vitalijus Karabanovas,
• Marius Stasys,
• Greta Jarockyte,
• Vilius Poderys,
• Simas Sakirzanovas and
• Ricardas Rotomskis

Beilstein J. Nanotechnol. 2017, 8, 1815–1824, doi:10.3762/bjnano.8.183

• behavior in biological systems and biocompatibility/nanotoxicity is still limited. The study of Cascales et al. showed that ultrasmall Yb:Er:NaGd(WO4)2 UCNPs could be successfully covered with Tween 80 and are internalized by human mesenchymal stem cells without triggering their metabolic activity, but

Micro- and nano-surface structures based on vapor-deposited polymers

• Hsien-Yeh Chen

Beilstein J. Nanotechnol. 2017, 8, 1366–1374, doi:10.3762/bjnano.8.138

• cell pluripotency against mouse embryonic stem cells [72]. A plasma-polymerized surface with gradient amino functionality was demonstrated to generate density gradients of individual gold (Au) and silver (Ag) nanoparticles on the surfaces [73]. Poly(p-xylylene) surfaces with continuously and counter

• proliferation (FGF-2) and osteogenic differentiation (BMP-2) for adipose-derived stem cells [76]. Selective deposition The aforementioned methods rely on physical means to obtain spatially controlled surface modifications and patterned structures. A simpler approach is the selective inhibition of the vapor

Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery

• Liga Saulite,
• Dominyka Dapkute,
• Karlis Pleiko,
• Ineta Popena,
• Simona Steponkiene,
• Ricardas Rotomskis and
• Una Riekstina

Beilstein J. Nanotechnol. 2017, 8, 1218–1230, doi:10.3762/bjnano.8.123

• nanoparticles in imaging and targeted therapy of tumours. Due to their tumour-homing ability, nano-engineered mesenchymal stem cells (MSCs) could be utilized as vectors to deliver diagnostic and therapeutic nanoparticles into a tumour. In the present study, uptake and functional effects of carboxyl-coated

• suggest that QD-labelled MSCs could be used for targeted drug delivery studies. Keywords: endocytosis; mesenchymal stem cells; quantum dots; stem cell differentiation; Introduction Despite remarkable advances in targeted therapies of various human malignancies, cancer is one of the leading causes of

• drug carriers [3]. Recent studies have shown that nano-engineered mesenchymal stem cells (MSCs) could be used as tumour-targeted therapeutic carriers, reflecting their tumour-homing capabilities [4][5][6]. MSCs are present in many tissues of the human body, including bone marrow, adipose tissues, skin

Uptake of the proteins HTRA1 and HTRA2 by cells mediated by calcium phosphate nanoparticles

• Olga Rotan,
• Katharina N. Severin,
• Simon Pöpsel,
• Alexander Peetsch,
• Melisa Merdanovic,
• Michael Ehrmann and
• Matthias Epple

Beilstein J. Nanotechnol. 2017, 8, 381–393, doi:10.3762/bjnano.8.40

• humidified atmosphere and cultivated according to standard cell culture protocols. A primary cell culture of human mesenchymal stem cells (hMSCs) was cultivated using mesenchymal stem cell (MSC) growth medium, supplemented according to the standard cultivation protocol. Approximately 12 h prior to the

Influence of hydrothermal synthesis parameters on the properties of hydroxyapatite nanoparticles

• Sylwia Kuśnieruk,
• Jacek Wojnarowicz,
• Agnieszka Chodara,
• Tadeusz Chudoba,
• Stanislaw Gierlotka and
• Witold Lojkowski

Beilstein J. Nanotechnol. 2016, 7, 1586–1601, doi:10.3762/bjnano.7.153

• cells and osteosarcoma cells) [10]. The cell culture experiment confirmed that in comparison to conventional HAp, cytophilicity of the nanophase mineral improved with nano-HAp. In addition, an increased viability and spread of stem cells was observed for nano-HAP, in particular for the smallest 20 nm

• proliferation of such malignant cells was inhibited more efficiently by the occurrence of the nanoscale effect than by HAp particle morphology [9]. Another study analyzed the effects of different sized nano-HAp – ranging from 20 to 80 nm – on the proliferation of bone-related cells (bone marrow mesenchyme stem

On the pathway of cellular uptake: new insight into the interaction between the cell membrane and very small nanoparticles

• Claudia Messerschmidt,
• Daniel Hofmann,
• Anja Kroeger,
• Katharina Landfester,
• Volker Mailänder and
• Ingo Lieberwirth

Beilstein J. Nanotechnol. 2016, 7, 1296–1311, doi:10.3762/bjnano.7.121

• : ATP depletion; calcium crystallization; cytotoxicity; endocytosis; HeLa cells; LDH; mesenchymal stem cells; morphology; necrosis; particle size; silica nanoparticles; TEM; Introduction Silicon dioxide nanoparticles (SiNPs) are used in a wide range of commercially available products to improve product

• limited to HeLa cells only or if this is a universal mechanism with which a cell and its membrane will react upon treatment with small silica NPs. Accordingly, we tested another 4 cell lines for the uptake morphologies: primary human mesenchymal stem cells (hMSC), human bone osteosarcoma cells (U2OS

Multiwalled carbon nanotube hybrids as MRI contrast agents

• Nikodem Kuźnik and
• Mateusz M. Tomczyk

Beilstein J. Nanotechnol. 2016, 7, 1086–1103, doi:10.3762/bjnano.7.102

• their potential as CAs exclusively in one of the MRI modes (T1 or T2). Further requirements consisted in better biocompatibility with the targeting of tumor cells, coupling with stem cells as well as crossing the cell membrane and blood–brain barrier. Finally, involving CNT activity in other diagnostic

• samples in several, especially biocompatible, media, such as water, saline, buffers, plasma, serum, or even cell cultures [18][33][34]. Stable dispersion is obtained by at least several minutes of sonication. Wu proved the stability of SPIO/oMWCNT#Wu in water for two weeks [38]. Models with stem cells

• ligand was coupled with a lipid chain, which was expected to enhance adsorption on the surface of the nanotube. The heptadentate DTPA ligand (L1), in turn, secured permanent coordination of Gd3+ in the new hybrid Gd-L1/MWCNT#Richard. Vittorio non-covalently combined pristine MWCNT with mesenchymal stem

Improved biocompatibility and efficient labeling of neural stem cells with poly(L-lysine)-coated maghemite nanoparticles

• Igor M. Pongrac,
• Marina Dobrivojević,
• Lada Brkić Ahmed,
• Michal Babič,
• Miroslav Šlouf,
• Daniel Horák and
• Srećko Gajović

Beilstein J. Nanotechnol. 2016, 7, 926–936, doi:10.3762/bjnano.7.84

• . Their properties can be modified by coating with different biocompatible polymers. To test if a coating polymer, poly(L-lysine), can improve the biocompatibility of nanoparticles applied to neural stem cells, poly(L-lysine)-coated maghemite nanoparticles were prepared and characterized. We evaluated

• their cellular uptake, the mechanism of internalization, cytotoxicity, viability and proliferation of neural stem cells, and compared them to the commercially available dextran-coated nanomag®-D-spio nanoparticles. Results: Light microscopy of Prussian blue staining revealed a concentration-dependent

• intracellular uptake of iron oxide in neural stem cells. The methyl thiazolyl tetrazolium assay and the calcein acetoxymethyl ester/propidium iodide assay demonstrated that poly(L-lysine)-coated maghemite nanoparticles scored better than nanomag®-D-spio in cell labeling efficiency, viability and proliferation

Nanostructured surfaces by supramolecular self-assembly of linear oligosilsesquioxanes with biocompatible side groups

• Maria Nowacka,
• Anna Kowalewska and
• Tomasz Makowski

Beilstein J. Nanotechnol. 2015, 6, 2377–2387, doi:10.3762/bjnano.6.244

• underlying matrix. For example, surfaces carrying COOH groups were applied for studies on the effect of surface wettability on protein adsorption and adhesion of human umbilical vein endothelial cells (HUVECs) and HeLa cells [3], human fibroblasts [14], human mesenchymal stem cells [15][22], corneal

Synthesis, characterization and in vitro effects of 7 nm alloyed silver–gold nanoparticles

• Simon Ristig,
• Svitlana Chernousova,
• Wolfgang Meyer-Zaika and
• Matthias Epple

Beilstein J. Nanotechnol. 2015, 6, 1212–1220, doi:10.3762/bjnano.6.124

• ) showed spherical, monodisperse, colloidally stable silver–gold nanoparticles of ≈7 nm diameter with measured molar metal compositions very close to the theoretical values. The examination of the nanoparticle cytotoxicity towards HeLa cells and human mesenchymal stem cells (hMSCs) showed that the toxicity

• can be verified. Cell culture experiments To examine the cytotoxicity with regards to the molar fraction of silver in the nanoparticles, HeLa cells and human mesenchymal stem cells were incubated with nanoalloys of nine different compositions and also with pure gold and pure silver nanoparticles. In

• cells) and human mesenchymal stem cells (hMSCs) were used for cell experiments. The HeLa cells were cultured in DMEM (Dulbecco's Modified Eagle's Medium), supplemented with 10% of fetal bovine serum (FBS), 100 U mL−1 penicillin, and 100 U mL−1 streptomycin. The hMSCs were cultivated in RPMI 1640

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

• effect was caused by silver ions. However, it supports findings made on spermatogonial stem cells in vitro, which claimed a decrease in cell proliferation after AgNP exposure [40][41]. Observations concerning female reproductive organs are rather rare as most nanoparticle biodistribution studies have

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

• stretching vibration of Si–O–Si. The FITC conjugation with hybrid NPs was studied by using fluorescence spectroscopy. Both FITC and FITC-γ-Fe2O3 NPs exhibited an emission peak at 516 nm. The biocompatibility of these hybrid NPs was observed by incubating rat mesenchymal stem cells (rMSCs) with these hybrid

• 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

• . Further, the adverse effects of these nanocomposites on the functions of stem cells were examined on adipocytes and osteocytes. Such strategies were also followed by Teng et al. [62], Kim et al. [63], Lee et al. [64], Shen et al. [65]. Further, Nagao et al. [66] reported the synthesis of a hybrid

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

• therapy and nanoparticles promises to enhance the effect of cellular therapies by using nanocarriers as drug delivery devices to guide the further differentiation or homing of stem cells. The impact of nanoparticles on primary cell types remains much more elusive as most groups study the nanoparticle–cell

• interaction in malignant cell lines. Here, we report on the influence of polymeric nanoparticles on human hematopoietic stem cells (hHSCs) and mesenchymal stem cells (hMSCs). In this study we systematically investigated the influence of polymeric nanoparticles on the cell functionality and differentiation

• capacity of hHSCs and hMSCs to obtain a deeper knowledge of the interaction of stem cells and nanoparticles. As model systems of nanoparticles, two sets of either bioinert (polystyrene without carboxylic groups on the surface) or biodegradable (PLLA without magnetite) particles were analyzed. Flow

Proinflammatory and cytotoxic response to nanoparticles in precision-cut lung slices

• Stephanie Hirn,
• Nadine Haberl,
• Kateryna Loza,
• Matthias Epple,
• Wolfgang G. Kreyling,
• Barbara Rothen-Rutishauser,
• Markus Rehberg and
• Fritz Krombach

Beilstein J. Nanotechnol. 2014, 5, 2440–2449, doi:10.3762/bjnano.5.253

• response in PCLS. However, these NPs induced cytotoxicity in human mesenchymal stem cells and peripheral blood mononuclear cells in vitro when incubated at a concentration of 25 µg/mL or higher [29][30]. Additionally, these NPs elicited a cytotoxic and inflammatory response in rat lungs 24 h after

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

• [36][37] used as macrophage surrogates. THP-1 is a cell line from the blood of a boy who suffered from acute monocytic leukemia. Childhood myelomonocytic leukemia is an aggressive clonal disease of pluripotent stem cells, which is clinically characterized by overproduction of monocytic cells that can

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

• surface functionalizations and investigated their interactions with various human cell lines, in particular HeLa cells and mesenchymal stem cells (MSCs). Of note, these studies were carried out in phosphate buffered saline (PBS), pH 7.4, or serum-free DMEM, so that we could probe interactions between

• NPs by mesenchymal stem cells (MSCs) in PBS solution. Because the initial step of endocytosis, i.e., the encounter of the NP with the cell membrane, is expected to be sensitive to the NP surface functionalization, we have exposed MSCs to two types of well-defined, positively charged PS NPs with

Biopolymer colloids for controlling and templating inorganic synthesis

• Laura C. Preiss,
• Katharina Landfester and
• Rafael Muñoz-Espí

Beilstein J. Nanotechnol. 2014, 5, 2129–2138, doi:10.3762/bjnano.5.222

• phosphate/chitosan composite films were shown to influence the behavior of human mesenchymal stem cells. Lee et al. [79] studied the scaffold–cell interaction by changing the crystallinity and ratio of the calcium phosphate. Alginate is another of the gelling biopolymers used as a scaffold. An alginate

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

• both ionic and nanoparticulate silver on the differentiation of human mesenchymal stem cells (hMSCs) into adipogenic, osteogenic and chondrogenic lineages and on the secretion of the respective differentiation markers adiponectin, osteocalcin and aggrecan. Results: As shown through laser scanning

• -toxic concentrations. Therefore, more studies are needed to investigate the effects of silver species on cells at low concentrations during long-term treatment. Keywords: differentiation; differentiation marker; mesenchymal stem cells; nanoparticles; silver; Introduction Novel nanomaterials are being

• healing [8]. In our previous studies on the biological effects of Ag-NP (PVP-coated, 80 nm) on human mesenchymal stem cells (hMSCs), we have shown that cell activation could occur at elevated but non-toxic silver concentrations [9][10]. In addition, we have shown that hMSCs are able to ingest Ag-NP

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

• 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

Imaging the intracellular degradation of biodegradable polymer nanoparticles

• Anne-Kathrin Barthel,
• Martin Dass,
• Melanie Dröge,
• Jens-Michael Cramer,
• Daniela Baumann,
• Markus Urban,
• Katharina Landfester,
• Volker Mailänder and
• Ingo Lieberwirth

Beilstein J. Nanotechnol. 2014, 5, 1905–1917, doi:10.3762/bjnano.5.201

• biological environments, intracellular degradation processes have been examined only to a very limited extent. PLLA nanoparticles with an average diameter of approximately 120 nm were decorated with magnetite nanocrystals and introduced into mesenchymal stem cells (MSCs). The release of the magnetite

• ., number of detached magnetite crystals, and the number of nanoparticles in one endosome), we demonstrate the importance of TEM studies for such applications in addition to fluorescence studies (flow cytometry and confocal laser scanning microscopy). Keywords: biodegradation; mesenchymal stem cells; PLLA

• expected for the measured fluorescence intensity when compared to that measured. The majority of measured intensities lie below the expected values. Parallel to each cell experiment, the doubling time of our respective mesenchymal stem cells was determined to be 48 h in the presence of the respective PLLA

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

• expression of genes responding to oxidative stress were observed [73]. However, Xing et al. [74] observed that embryonic stem cells responded to incubation with NDs with an increased expression of MOGG-1 and P53, which are proteins related to DNA repair processes. This genotoxicity was increased when cells

• interpret these results in terms of a possible application for neural stimulation. Graphene-based substrates have also been investigated as scaffolds for growth and for the differentiation of stem cells [142][143]. The differentiation into neurons of human neural stem cells (hNSCs), cultured on graphene has

• nanogrids, further enhanced by means of a repeated photo stimulation. Li and co-workers [146] designed a three-dimensional graphene foam scaffold for neural stem cells. This scaffold allowed the formation of a three-dimensional neural network, resulting in an excellent substrate for cell adhesion and

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

• the modified particles were characterized by transmission electron microscopy and dynamic light scattering with regard to morphology, particle size and polydispersity. In vitro survival of human stem cells was then investigated by using the methyl thiazolyl tetrazolium (MTT) assay, which showed that D

• -mannose- and poly(N,N-dimethylacrylamide)-coated γ-Fe2O3 particles exhibit much lower level of cytotoxicity than the non-coated γ-Fe2O3. Keywords: maghemite; magnetic; MTT assay; nanoparticles; stem cells; Introduction One of the most important applications of nanoparticles in biomedicine is the direct

• labeling of cells in order to track them both in diagnostics and therapeutics [1][2]. For example, mesenchymal [3], neural [4], and bone marrow [5] stem cells, as well as other cells are widely labeled by surface-coated iron oxide nanoparticles. Other applications of nanoparticles involve the delivery of

Influence of the PDMS substrate stiffness on the adhesion of Acanthamoeba castellanii

• Sören B. Gutekunst,
• Carsten Grabosch,
• Alexander Kovalev,
• Stanislav N. Gorb and
• Christine Selhuber-Unkel

Beilstein J. Nanotechnol. 2014, 5, 1393–1398, doi:10.3762/bjnano.5.152

• and position themselves [6]. Once grown on a substrate with defined elasticity, cells adapt their own elasticity to the elasticity of their environment [7]. But not only differentiated cells are influenced by substrate stiffness. For stem cells it has been demonstrated that their differentiation is

• substrate. The increase of adhesion area with decreasing Young`s modulus is opposite to the behavior of human mesenchymal stem cells [33] but is in good agreement with the trend observed in studies on neural stem cell cultures [34]. This result is reasonable, as during the infection process, A. castellanii