Entry of nanoparticles into cells and tissues: status and challenges

• Kirsten Sandvig,
• Tore Geir Iversen and
• Tore Skotland

Beilstein J. Nanotechnol. 2024, 15, 1017–1029, doi:10.3762/bjnano.15.83

• Nanoparticle Uptake The complexity of endocytosis The field of endocytosis has undergone a remarkable development during the last decades. Today it is clear that there is a variety of uptake mechanisms in cells, and adding to the complexity, they are partially cell-type specific [7][8][9][10]. In Figure 1, we

• shown to be internalized by different endocytic mechanisms [58][59][60]. Uptake via caveolae may be a minor route; introduction of caveolae in Caco-2 cells by transfection with caveolin did not increase the uptake of cholera toxin [58]. Macropinocytosis and nanoparticle uptake Several of the NPs studied

• not succeed in killing the cell, one may end up with stimulating cancer cell growth, and not at all with the intended outcome. Clathrin-mediated endocytosis and nanoparticle uptake Clathrin-mediated endocytosis can function as an efficient uptake mechanism for relatively small molecules and NPs. The

Assessing phytotoxicity and tolerance levels of ZnO nanoparticles on Raphanus sativus: implications for widespread adoptions

• Pathirannahalage Sahan Samuditha,
• Nadeesh Madusanka Adassooriya and
• Nazeera Salim

Beilstein J. Nanotechnol. 2024, 15, 115–125, doi:10.3762/bjnano.15.11

• nanoparticle uptake, transport, and bioaccumulation in the food chain when ZnO NPs reach the soil, which positively or negatively affects plant growth and productivity [16]. For instance, ZnO NPs at an optimum concentration of 0.13 g/L promoted seed germination and root growth of groundnut (Arachis hypogaea L

pH-driven enhancement of anti-tubercular drug loading on iron oxide nanoparticles for drug delivery in macrophages

• Karishma Berta Cotta,
• Sarika Mehra and
• Rajdip Bandyopadhyaya

Beilstein J. Nanotechnol. 2021, 12, 1127–1139, doi:10.3762/bjnano.12.84

• drug and nanoparticle uptake in macrophage cells in vitro, as macrophages are the primary site of infection for many intracellular pathogens including Mycobacterium [31]. Results and Discussion Iron oxide nanoparticles were successfully synthesized, indicated by the appearance of a black coloration

• release medium). Drug and nanoparticle uptake in macrophages THP1 cells, a monocyte cell line, was differentiated into macrophage cells through a treatment with 25 ng/mL of phorbol 12-myristate acetate (PMA), for 24 h, at 37 °C and 5% CO2. Post incubation, PMA was washed off and fresh RPMI-1640

• free drug, dashed lines – for nanoparticles). The standard deviation plotted for each data point is obtained from 3 replicates each. (a) NOR uptake in macrophage cells after 48 h treatment with NOR, extracellular concentration of 32 µg/mL. (b) Nanoparticle uptake estimated in terms of the uptake of Fe

Comprehensive review on ultrasound-responsive theranostic nanomaterials: mechanisms, structures and medical applications

• Sepand Tehrani Fateh,
• Lida Moradi,
• Elmira Kohan,
• Michael R. Hamblin and
• Amin Shiralizadeh Dezfuli

Beilstein J. Nanotechnol. 2021, 12, 808–862, doi:10.3762/bjnano.12.64

Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization

• Barbora Svitkova,
• Vlasta Zavisova,
• Veronika Nemethova,
• Martina Koneracka,
• Miroslava Kretova,
• Filip Razga,
• Monika Ursinyova and
• Alena Gabelova

Beilstein J. Nanotechnol. 2021, 12, 270–281, doi:10.3762/bjnano.12.22

• .12.22 Abstract The efficient entry of nanotechnology-based pharmaceuticals into target cells is highly desired to reach high therapeutic efficiency while minimizing the side effects. Despite intensive research, the impact of the surface coating on the mechanism of nanoparticle uptake is not sufficiently

• carrier, are the most frequently used materials for biomedical applications [17][18][19][20]. The impact of the surface chemistry on the mechanism of nanoparticle uptake has not been sufficiently clarified yet. MNPs with comparable basic physicochemical characteristics (e.g., particle size, surface charge

Interactions at the cell membrane and pathways of internalization of nano-sized materials for nanomedicine

• Valentina Francia,
• Daphne Montizaan and
• Anna Salvati

Beilstein J. Nanotechnol. 2020, 11, 338–353, doi:10.3762/bjnano.11.25

• . Keywords: cell receptors; drug targeting; endocytosis; nanoparticle corona; nanoparticle uptake; Introduction Nano-sized materials are widely studied in nanomedicine for their potential use as drug carriers, in imaging, and for diagnostic purposes [1][2][3]. Because of their size, they can interact with

• carried out by altering cellular pathways using different methods in order to determine their involvement in nanoparticle uptake. However, it is well established that perturbation of a cellular mechanism might as well lead to the alteration of other mechanisms. Therefore, when performing such studies, it

• proteins are instead overexpressed, in order to eventually detect an increase in nanoparticle uptake [17]. Nevertheless, also these methods might lead to artefacts, since the overexpression might induce the activation of a pathway that may not be active under physiological conditions [22][214]. Furthermore

The different ways to chitosan/hyaluronic acid nanoparticles: templated vs direct complexation. Influence of particle preparation on morphology, cell uptake and silencing efficiency

• Arianna Gennari,
• Julio M. Rios de la Rosa,
• Erwin Hohn,
• Maria Pelliccia,
• Enrique Lallana,
• Roberto Donno,
• Annalisa Tirella and
• Nicola Tirelli

Beilstein J. Nanotechnol. 2019, 10, 2594–2608, doi:10.3762/bjnano.10.250

• the different preparative processes may affect nanoparticle uptake and the release of encapsulated payloads using a murine macrophagic (RAW 264.7) and a human colorectal tumor (HCT-116) cell line, both popular in vitro models for the study of cellular interactions of HA-based materials [20][22

• -based cationic nanocarriers [40][41]. Next, we analysed the nanoparticle uptake in the two cell lines for up to 24 h; we tracked the fluorescence associated to nanoparticles in cell lysates, which accounts for both membrane-bound and internalized materials [10]. We used fluorescently labelled chitosan

• ) the irrelevance of the HA corona for the nanoparticle uptake, and the slightly poorer performance of templated particles in silencing. However, one should extrapolate the irrelevance of HA corona for cell–nanoparticle interactions: in a previous study we have demonstrated that it does allow for a

Effects of gold and PCL- or PLLA-coated silica nanoparticles on brain endothelial cells and the blood–brain barrier

• Aniela Bittner,
• Angélique D. Ducray,
• Hans Rudolf Widmer,
• Michael H. Stoffel and
• Meike Mevissen

Beilstein J. Nanotechnol. 2019, 10, 941–954, doi:10.3762/bjnano.10.95

• metabolic state of cells have to be further characterized before use for medical purposes. Keywords: blood–brain barrier; laser tissue soldering; nanomedicine; nanoparticle uptake; rBCEC4 cells; Introduction Nanotechnology is commonly used in various fields, such as agriculture and pharmaceutical industry

• was removed and the remaining MTT-formazan was dissolved in DMSO (Sigma, Switzerland). Absorbance was measured at 540 nm using a plate reader (Synergy HT, BioTek, Switzerland). Nanoparticle uptake PCL-, PLLA- and Au-NP uptake was investigated using transmission electron microscopy (TEM). PCL- and PLLA

Polydopamine-coated Au nanorods for targeted fluorescent cell imaging and photothermal therapy

• Boris N. Khlebtsov,
• Andrey M. Burov,
• Timofey E. Pylaev and
• Nikolai G. Khlebtsov

Beilstein J. Nanotechnol. 2019, 10, 794–803, doi:10.3762/bjnano.10.79

• -functionalized nanoparticles in folate-positive HeLa cells in contrast to the folate-negative HEK 293 cells using fluorescent microscopy. The replacement of folic acid with polyethylene glycol (PEG) leads to a decrease in nanoparticle uptake by both folate-positive and folate-negative cells. We performed NIR

• plasmonic photothermal therapy. In this work we utilized fluorescent properties of our nanocomposites to study the folate-mediated nanoparticle uptake. Folate-positive HeLa and folate-negative HEK 293 cell lines were used as models. PEGylated AuNRs-PDA-R123-PEG particles were used as a reference to estimate

Targeting strategies for improving the efficacy of nanomedicine in oncology

• Gonzalo Villaverde and
• Alejandro Baeza

Beilstein J. Nanotechnol. 2019, 10, 168–181, doi:10.3762/bjnano.10.16

• potent estrogen receptor modulator tamoxifen [26]. These nanoparticles were capable to induce a significant in vivo tumour growth inhibition due to the enhanced nanoparticle uptake within the tumoral cells owing to the strong interaction between the antibody and HER2. Another interesting possibility is

A comparative study of the nanoscale and macroscale tribological attributes of alumina and stainless steel surfaces immersed in aqueous suspensions of positively or negatively charged nanodiamonds

• Colin K. Curtis,
• Antonin Marek,
• Alex I. Smirnov and
• Jacqueline Krim

Beilstein J. Nanotechnol. 2017, 8, 2045–2059, doi:10.3762/bjnano.8.205

• (SEM) measurements were employed to assess nanoparticle uptake, surface polishing, and resistance to solid–liquid interfacial shear motion. The QCM studies revealed abrupt changes to the surfaces of both alumina and stainless steel upon injection of –ND into the surrounding water environment that are

Uptake and intracellular accumulation of diamond nanoparticles – a metabolic and cytotoxic study

• Antonín Brož,
• Lucie Bačáková,
• Pavla Štenclová,
• Alexander Kromka and
• Štěpán Potocký

Beilstein J. Nanotechnol. 2017, 8, 1649–1657, doi:10.3762/bjnano.8.165

• µg/mL, 300 µg/cm2). Live-cell imaging of diamond nanoparticle uptake Live-cell imaging (see Supporting Information File 1 and Supporting Information File 2 for full experimental data) confirmed the formation of DND aggregates in the suspension (10 µg/mL, 3 µg/cm2). Particle aggregates are collected

Low uptake of silica nanoparticles in Caco-2 intestinal epithelial barriers

• Dong Ye,
• Mattia Bramini,
• Delyan R. Hristov,
• Sha Wan,
• Anna Salvati,
• Christoffer Åberg and
• Kenneth A. Dawson

Beilstein J. Nanotechnol. 2017, 8, 1396–1406, doi:10.3762/bjnano.8.141

• combination of imaging, flow cytometry and transport studies. Compared to typical observations in standard cell lines commonly used for in vitro studies, silica nanoparticle uptake into well-developed Caco-2 cellular barriers was found to be very low. Instead, nanoparticle association to the apical outer

• transport through them. Keywords: Caco-2; differentiation and polarisation; epithelial cell barrier; microscopy imaging; particle interaction; uptake and localisation; Introduction An overall conclusion from a multitude of nanoparticle-cell in vitro studies is that nanoparticle uptake into cells is

• overall barrier integrity. Nanoparticle uptake in Caco-2 barriers cultured for 4 and 21 days Flow cytometry was used to quantify cell fluorescence intensity due to association of the fluorescent SiO2-NPs with the cells. In order to test if cell polarisation/differentiation plays a role in controlling

Bright fluorescent silica-nanoparticle probes for high-resolution STED and confocal microscopy

• Isabella Tavernaro,
• Christian Cavelius,
• Henrike Peuschel and
• Annette Kraegeloh

Beilstein J. Nanotechnol. 2017, 8, 1283–1296, doi:10.3762/bjnano.8.130

• suitable for biological nanoparticle uptake experiments and have been used to determine the intracellular migration and nuclear penetration after uptake into Caco-2 cells [44]. They have also been used to analyse their intracellular agglomeration and their association with intracellular vesicles in living

• low tendency to agglomerate, which makes them suitable for biological nanoparticle uptake experiments. Not only allows the presented synthesis method for the embedding of different kinds of fluorophores (proteins, quantum dots or metallic nanoclusters), but the method also provide the option to gain

• and the refractive index of the solvent, respectively [56]. When performing this type of comparative measurement, all the measurement parameters were identical for the reference sample and the sample to be tested. Exposure of cells to NPs and preparation of samples for microscopy Nanoparticle uptake

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

• laser beam, the intensity of which is proportional to the intracellular density and therefore reflects the nanoparticle uptake, we were able to detect the presence of nanoparticles in NSC. The percentage of nanoparticle-positive cells was determined using the Overtone cumulative histogram subtraction

• process, e.g., macropinocytosis, was the mechanism of nanoparticle uptake for both types of nanoparticles. NSC progenitor post-labeling phenotype and neural differentation potential NSCs treated with PLL-γ-Fe2O3 and nanomag®-D-spio nanoparticles for 48 h stained positive for nestin, a marker of neural

• , evaluation of nanoparticle uptake efficiency and defining the mechanism of nanoparticle uptake by NSCs, an Attune® acoustic focusing flow cytometer (Applied Biosystems, USA) containing a 488 nm laser, a forward-scatter (FSC) light diode detector and a photomultiplier tube of the side-scattered (SSC) light

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

• . Additionally, membrane wrapping, which has been described as an important step in nanoparticle uptake [67] cannot be performed by spermatozoa due to their rather rigid and tensely streched plasma membrane. Another noteworthy point is the variation observed in our experiments concerning nanoparticle attachement

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

• filter (7-AAD or APC). The cells were analyzed by gating on a dotplot of the forward/sideward scatter and thereby excluding free particles and cell debris. The nanoparticle uptake was analyzed in a PMI channel histogram, and the 7-AAD signal in a 7-AAD/PMI channel dotplot by setting three gates (vital

• by Tukey’s Multiple Comparison Test (GraphPad Prism 5, GraphPad Software Inc., USA). Statistical differences of p < 0.05 were considered significant. Significance is indicated in the figures as follows: p > 0.05 ns (not significant), p < 0.05 *, p < 0.01 **, and p < 0.001 ***. (A) Nanoparticle uptake

Biological responses to nanoscale particles

• Reinhard Zellner

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

• 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

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

• different nanoparticle formulations, we used different inhibitors to block the best-known internalization routes: clathrin-mediated, caveolae-mediated and macropinocytosis [46]. Microscopy data and the semi-quantitative analysis of the nanoparticle uptake behavior revealed a caveolae-dependent

• human alveolar epithelial cell line A549 showed no nanoparticle uptake after the inhibition of caveolae- and clathrin-mediated endocytosis [62]. Such a cell-type-specific internalization was also demonstrated in our study due to the inhibition of several endocytosis mechanisms. We showed that the mouse

• derived cell line SVEC4-10 used clathrin- and macropinocytosis for the nanoparticle uptake. In contrast, the used human endothelial cell line HMEC-1 internalized different nanoparticle formulations via caveolae. Another interesting aspect is that nanoparticle uptake also depends on the nanoparticle size

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

• 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

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

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

• uptake of basolaterally applied particles, since MDCK II cells exhibit caveolae on the basolateral side [17]. However, the immobilization of the particles on the substrate could not be overcome by the cell (see discussion above). Hence, we conclude that there is no significant basolateral nanoparticle

• uptake from patterned substrates, which implies that nanoparticle removal from implants by epithelial cells is negligible. Concerning cytotoxicity, apical exposure of CTAB nanorods reduced mitochondrial activity compared to untreated cells, whereas PEG nanorods showed no impact, regardless of end group

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

• leukemia cells, whether differentiated or not [43]. Interestingly, also the surface functionalization affected the rate and amount of nanoparticle uptake. Because the uptake mechanism used by the cells was also different for buffer and serum-containing medium, it was obvious that opsonization played a

The gut wall provides an effective barrier against nanoparticle uptake

• Heike Sinnecker,
• Thorsten Krause,
• Sabine Koelling,
• Ingmar Lautenschläger and
• Andreas Frey

Beilstein J. Nanotechnol. 2014, 5, 2092–2101, doi:10.3762/bjnano.5.218

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

• further studies are needed to reveal the molecular uptake mechanism(s). FIB/SEM analysis represents a valuable technique to proof the nanoparticle uptake as was similarly shown by Pelka et al. [85] with HT29 cells (colon carcinoma cells) and platinum nanoparticles. Thus, FIB/SEM which presents a technique