Key for crossing the BBB with nanoparticles: the rational design

• Sonia M. Lombardo,
• Marc Schneider,
• Akif E. Türeli and
• Nazende Günday Türeli

Beilstein J. Nanotechnol. 2020, 11, 866–883, doi:10.3762/bjnano.11.72

• Central nervous system diseases are a heavy burden on society and health care systems. Hence, the delivery of drugs to the brain has gained more and more interest. The brain is protected by the blood–brain barrier (BBB), a selective barrier formed by the endothelial cells of the cerebral microvessels

• damaged by ischemia [2]. One of the main limitations for the treatment of neurological disorders is the difficulty to deliver drugs to the brain. The brain is surrounded by the blood–brain barrier (BBB), a selective barrier formed by the endothelial cells of the cerebral microvessels [3][4]. The surface

• function, the BBB has a unique anatomy. The brain endothelial cells are joined by tight junctions and do not present fenestrations [5][6][7][8]. The endothelial cells are surrounded firstly by a discontinuous layer of pericytes and secondly by the basal lamina, adjacent to the astrocyte feet (Figure 1

Identification of physicochemical properties that modulate nanoparticle aggregation in blood

• Ludovica Soddu,
• Duong N. Trinh,
• Eimear Dunne,
• Dermot Kenny,
• Giorgia Bernardini,
• Ida Kokalari,
• Arianna Marucco,
• Marco P. Monopoli and
• Ivana Fenoglio

Beilstein J. Nanotechnol. 2020, 11, 550–567, doi:10.3762/bjnano.11.44

• activation of some factors by surface-driven exposure of cryptic domains following adsorption was reported in some studies [5][6]. Other studies have reported the NPs ability to damage or activate platelets, endothelial cells or monocytes [4]. Some physicochemical properties, including the surface charge and

• platelets [16]. Additionally, SNPs were found to induce pre-thrombotic states through surface-driven activation of the coagulation factor XII [17][18]. Finally, SNPs are known to induce oxidative stress in several cell lines including endothelial cells [19] and leucocytes [20][21], a process that in vivo

• . Platelet adhesion Activated platelets are physiologically programmed to adhere to the endothelial wall of damaged blood vessels. The VWF anchored to damaged endothelial cells plays a major role in this process, encouraging platelets to tether, roll and finally adhere at the site of damage. Dynamic platelet

Poly(1-vinylimidazole) polyplexes as novel therapeutic gene carriers for lung cancer therapy

• Gayathri Kandasamy,
• Elena N. Danilovtseva,
• Vadim V. Annenkov and
• Uma Maheswari Krishnan

Beilstein J. Nanotechnol. 2020, 11, 354–369, doi:10.3762/bjnano.11.26

• . Detailed synthesis and characterization of the polymer was earlier reported by Prof Annenkov [21]. The lung cancer cell line A549 was procured from the National Centre for Cell Sciences (NCCS), Pune. Human umbilical vein endothelial cells (HUVECs) were procured from ATCC, USA. EGMTM endothelial cell growth

• formation in the cells clearly indicating the effect of VEGF inhibition. Earlier studies have shown that VEGF binds to α9β1 integrin on the cell surface, which mediates the formation and migration of endothelial cells through Src and focal adhesion kinase [34]. Therefore, the silencing of VEGF retards tube

• through a PVI polyplex is effective in inhibiting tube formation in endothelial cells. Microarray analysis VEGF has been implicated in a variety of signaling pathways in cancer that are now being revealed through gene and protein expression studies. To identify the effect of VEGF silencing on the various

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

• , the role of caveolae in endocytosis is currently being debated. Some suggest that caveolae are involved in transcytosis in endothelial cells [100]. According to this hypothesis, caveolae rapidly detach from the apical side of the membrane and fuse with the basal one, or directly form transient pores

• in thin endothelial cells [101]. Other studies have shown that in many cell types caveolae are normally not involved in endocytosis, but are stable invaginations present at the cell surface [102][103], and only undergo endocytosis upon stimulation [96][104]. Apart from these mechanisms, phagocytosis

• nanomedicines, can end up in compartments other than the lysosomes. For example, in several reports it appears that nanoparticles can be transcytosed across endothelial cells [178][179]. However, the existence of a dedicated pathway, such as caveolae-mediated endocytosis, for transcytosis of macromolecules is

Rational design of block copolymer self-assemblies in photodynamic therapy

• Maxime Demazeau,
• Laure Gibot,
• Anne-Françoise Mingotaud,
• Patricia Vicendo,
• Clément Roux and
• Barbara Lonetti

Beilstein J. Nanotechnol. 2020, 11, 180–212, doi:10.3762/bjnano.11.15

• ) effect [2][3], constituted the triggering factor for the development of a whole new part of medicine, namely nanomedicine. Indeed, the observed spontaneous accumulation was explained by the existence of disjunctions between endothelial cells in the proximity of inflamed and cancerous tissues, which

Molecular architectonics of DNA for functional nanoarchitectures

• Debasis Ghosh,
• Lakshmi P. Datta and
• Thimmaiah Govindaraju

Beilstein J. Nanotechnol. 2020, 11, 124–140, doi:10.3762/bjnano.11.11

• construction of a DNA origami-based nanorobot for the cargo delivery of payloads into cancer cells [56]. The autonomous DNA nanorobot was constructed using a nucleolin-binding DNA aptamer and was loaded with thrombin protease. The nucleolin protein was overexpressed in tumor-associated endothelial cells, which

Internalization mechanisms of cell-penetrating peptides

• Ivana Ruseska and
• Andreas Zimmer

Beilstein J. Nanotechnol. 2020, 11, 101–123, doi:10.3762/bjnano.11.10

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

• are foreign objects, careful evaluation of their toxicological and functional aspects prior to medical application is imperative. In this study, we aimed to determine the effects of gold and polymer-coated silica nanoparticles used in laser tissue soldering on brain endothelial cells and the blood

• –brain barrier using rat brain capillary endothelial cells (rBCEC4). All types of nanoparticles were taken up time-dependently by the rBCEC4 cells, albeit to a different extent, causing a time- and concentration-dependent decrease in cell viability. Nanoparticle exposure did not change cell proliferation

• effects of various NPs on cells of the vasculature and the BBB need to be determined. The BBB is made of specialized endothelial cells (ECs), astrocytes and pericytes, forming a tight barrier, thus restricting access to the brain [14][15]. Disruption of this barrier allows potentially harmful molecules to

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

• to employ antibodies for the recognition of the tumoral blood vessels instead of the tumoral cells. Endoglin, or CD105, is a glycoprotein usually overexpressed on the surface of the endothelial cells which compose the tumoral vessels. TRC105 is a human/murine chimeric antibody which recognizes CD105

Preparation of micro/nanopatterned gelatins crosslinked with genipin for biocompatible dental implants

• Reika Makita,
• Tsukasa Akasaka,
• Seiichi Tamagawa,
• Yasuhiro Yoshida,
• Saori Miyata,
• Hirofumi Miyaji and
• Tsutomu Sugaya

Beilstein J. Nanotechnol. 2018, 9, 1735–1754, doi:10.3762/bjnano.9.165

• [45]. These micro/nanopillars, with diameters of 1 µm or 250 nm, increased the proliferation of endothelial cells better than a planar gelatin surface. Zorlutuna et al. have reported that a collagen surface with a nanogroove could be fabricated by crosslinking with carbodiimide [37][46]. This

• several types of cells, the grooves with widths ranging from submicrometers to several tens of micrometers can effectively maneuver to align the cells [57][58]. However, Zorlutuna et al. have reported that human microvascular endothelial cells were not aligned in collagen grooves with widths of 333, 500

• [45][46]. In one study, the cell proliferation of corneal endothelial cells on GelMA pillars with a diameter of 250 nm or 1 µm was found to be increased compared to the planar GelMA surface [45]. Zorlutuna et al. have also shown that cell proliferation of vascular smooth muscle cells in collagen

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

• potential along the bundle gel. Collagen-based helical nanofibrillar scaffolds have shown the ability to support the growth of human endothelial cells [104]. The nanofibrils were generated by applying shear stress on a collagen solution in a (chiral) nematic phase. When the cells were seeded in a 3D

Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages

• Dimitri Vanhecke,
• Dagmar A. Kuhn,
• Dorleta Jimenez de Aberasturi,
• Sandor Balog,
• Ana Milosevic,
• Dominic Urban,
• Diana Peckys,
• Niels de Jonge,
• Wolfgang J. Parak,
• Alke Petri-Fink and
• Barbara Rothen-Rutishauser

Beilstein J. Nanotechnol. 2017, 8, 2396–2409, doi:10.3762/bjnano.8.239

• microvascular endothelial cells via flotillin-mediated uptake [18]. Flotillin-mediated uptake was also observed for silica NPs in lung epithelial and endothelial cells [19]. The various uptake pathways have one aspect in common: The internalized NP is ultimately located in an intracellular vesicle. Endocytosis

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

• –Arg–Glu–Asp–Val (CREDV) peptide showed the synergic anti-fouling property and preferentially enhanced attachment of endothelial cells in such patterned areas [50]. In another report, a multifunctional coating was realized via CVD copolymerization to deposit a poly(p-xylylene) copolymer, which

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

• , experiments in HEK cells showed the uptake of carboxyl QDs through caveolin/lipid raft-mediated endocytosis; although it has been reported that caveolin-mediated endocytosis is the dominating uptake route in endothelial cells, smooth muscle cells and adipocytes [44][46]. Damalakiene et al. demonstrated that

Silicon microgrooves for contact guidance of human aortic endothelial cells

• Sara Fernández-Castillejo,
• Pilar Formentín,
• Úrsula Catalán,
• Josep Pallarès,
• Lluís F. Marsal and
• Rosa Solà

Beilstein J. Nanotechnol. 2017, 8, 675–681, doi:10.3762/bjnano.8.72

• cell adhesion, morphology and proliferation were assessed, by comparing them to flat silicon substrates, used as control condition. Using human aortic endothelial cells, microscopy images demonstrate that the cellular response is different depending on the silicon surface, when it comes to cell

• microscale features to mimic the endothelium in lineal vessels. Keywords: cell morphology; contact guidance; microgrooves; silicon; human aortic endothelial cells (HAECs); Introduction Micro- and nanostructured materials for medical devices have demonstrated that surface topography as well as surface

• the affinity of the cell to be elongated and guided by the shape of the surface. The response of the cells to these topographical cues and the concept of contact guidance have been described previously for a wide variety of cells such as neuronal, epithelial or endothelial cells [8][9][10]. In

Nano- and microstructured materials for in vitro studies of the physiology of vascular cells

• Alexandra M. Greiner,
• Adria Sales,
• Hao Chen,
• Sarah A. Biela,
• Dieter Kaufmann and
• Ralf Kemkemer

Beilstein J. Nanotechnol. 2016, 7, 1620–1641, doi:10.3762/bjnano.7.155

• ) and endothelial cells (ECs) with materials having micro- and nanostructured surfaces. We summarize fabrication techniques for surface topographies, materials, geometries, biochemical functionalization, and mechanical properties of such materials. Furthermore, various studies on vascular cell behavior

• potential interesting future studies. Keywords: fabrication methods; materials selection; nano- and micro-topography; vascular endothelial cells; vascular smooth muscle cells; Introduction Cells adhering to biomaterials are influenced by the surface topography, the surface chemistry and the mechanical

• discusses model studies with a special emphasis on the fabrication of substrates with well-defined nano- and microstructured surfaces for in vitro studies with vascular cells (Figure 1). Vascular endothelial cells (ECs) and smooth muscle cells (SMCs) are two vascular cell types forming blood vessels (Figure

Viability and proliferation of endothelial cells upon exposure to GaN nanoparticles

• Tudor Braniste,
• Ion Tiginyanu,
• Tibor Horvath,
• Simion Raevschi,
• Serghei Cebotari,
• Marco Lux,
• Axel Haverich and
• Andres Hilfiker

Beilstein J. Nanotechnol. 2016, 7, 1330–1337, doi:10.3762/bjnano.7.124

• Moldova 10.3762/bjnano.7.124 Abstract Nanotechnology is a rapidly growing and promising field of interest in medicine; however, nanoparticle–cell interactions are not yet fully understood. The goal of this work was to examine the interaction between endothelial cells and gallium nitride (GaN

• ) semiconductor nanoparticles. Cellular viability, adhesion, proliferation, and uptake of nanoparticles by endothelial cells were investigated. The effect of free GaN nanoparticles versus the effect of growing endothelial cells on GaN functionalized surfaces was examined. To functionalize surfaces with GaN, GaN

• nanoparticles were synthesized on a sacrificial layer of zinc oxide (ZnO) nanoparticles using hydride vapor phase epitaxy. The uptake of GaN nanoparticles by porcine endothelial cells was strongly dependent upon whether they were fixed to the substrate surface or free floating in the medium. The endothelial

Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

• Yue Zhang and
• Wan-Xi Yang

Beilstein J. Nanotechnol. 2016, 7, 675–684, doi:10.3762/bjnano.7.60

• approach for nanoparticles to penetrate endothelial layers and then have an impact on other tissues and organs. Keywords: blood vessels; endothelial cells; nanoparticles; oxidative stress; tight junction; Introduction Products related to nanoparticles (NPs) are increasingly growing in number. We can

• ]. Several modified NPs were also used in vascular-targeted therapy, which showed their way into endothelial cells and escape from the endosome in vitro [39]. Likewise, while iron oxide NPs are very helpful with their capability for imaging, their toxicity towards vascular endothelial cells cannot be ignored

• the inside, it can be simply summarized as pericytes and endothelial cells [46], even if distinct types of vessel hold differences in those layer structures. The endothelium cells, a sort of cell shared by all kinds of blood vessels, exhibit multiple interactions with NPs injected into vascular system

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

• epithelial cells [23], fibroblasts [24], myoblasts [25] and endothelial cells [26]. Substrates with COOH groups were also used to elucidate the role of chemistry-dependent differences in cell differentiation owing to specific binding to proteins adsorbed on the surface [25][27][28]. Well-defined substrates

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

• experiments by using primary human cell models of the blood system. Pristine NPs immediately affected the vitality of endothelial cells, triggered thrombocyte activation and aggregation, and resulted in hemolysis of erythrocytes. However, such pristine NPs existed only for a very brief period of time in the

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

• fluorescence studies. The size of the particles was found to be 31 ± 4 nm with an emission peak at approx. 620 nm. The in vitro studies with human umbilical vein endothelial cells (HUVEC) suggested that these NPs could be used simultaneously as fluorescent and MRI contrasting agent. 2.4 Manganese oxide as

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

• vitro mono- and complex coculture models (MC and CC) of the air–blood barrier. As alveolar epithelial cells we used A549 and ISO-HAS-1 as microvascular endothelial cells in a coculture model. To evaluate in what way and to what extent different aSNP-surface functionalisations play a role in their

• 10 days Dex was necessary to form confluent and close epithelial and endothelial monolayers as it is seen for NCI H441/ISO-HAS-1 coculture in our previous studies [8][9][11]. Additionally, Dex directly suppresses effectively angiogenesis in endothelial cells [18]. Thus, these effects come in handy

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

• 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

• , experiences a force of approximately 77 pN [5]. Finally, in many studies, endothelial cells are of special interest due to their outstanding role regarding the distribution of nanoparticles by the vascular system. Hence, another important issue is that a static medium is certainly not a physiological

• surrounding for these cells, which are exposed in vivo to shear rates of up to 3000 s−1 [6]. It was recently shown that the glycocalix of endothelial cells is substantially reorganized under shear [7] and several effects of shear stress on cellular uptake mechanisms have been reported [8][9][10]. One solution

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

• better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot) nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of

• endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA) leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to

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

Oxygen-plasma-modified biomimetic nanofibrous scaffolds for enhanced compatibility of cardiovascular implants

• Anna Maria Pappa,
• Varvara Karagkiozaki,
• Silke Krol,
• Spyros Kassavetis,
• Dimitris Konstantinou,
• Charalampos Pitsalidis,
• Lazaros Tzounis,
• Nikos Pliatsikas and
• Stergios Logothetidis

Beilstein J. Nanotechnol. 2015, 6, 254–262, doi:10.3762/bjnano.6.24

• case of cardiovascular implants, though, the successful revascularization after implantation remains an unmet clinical problem [11]. This implies that endothelial cells must properly attach and migrate into the surface of the implanted material in order to form an appropriate network that will enable