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

Fate and transformation of silver nanoparticles in different biological conditions

• Barbara Pem,
• Marija Ćurlin,
• Darija Domazet Jurašin,
• Valerije Vrček,
• Rinea Barbir,
• Vedran Micek,
• Raluca M. Fratila,
• Jesus M. de la Fuente and
• Ivana Vinković Vrček

Beilstein J. Nanotechnol. 2021, 12, 665–679, doi:10.3762/bjnano.12.53

• significantly affect AgNPs and determine their colloidal stability and cellular interactions as evidenced earlier [27][31][32][33]. In the acidic medium of the stomach, AgNPs both agglomerate and dissolve [15][26][34]. The transformation will likely be incomplete due to protein corona formation and short

• behaviour can be attributed to the loss of electrostatic repulsion between particles due to the complexation with counter ions present in media with high ionic strength [8][47]. The presence of proteins prevented AgNP agglomeration in m(CCM+BSA), m(CYS+BSA), m(GSH+BSA) due to the formation of protein corona

• AgNPs enter the body where they gain a protein corona, aggregate, and dissolve to Ag+. Ionic silver may precipitate in the anion-rich environment of different tissues, where Ag binds to S, resulting in nanocrystals. Aggregation and corona–NP destabilisation can also lead to precipitation. Whole blood

A review on nanostructured silver as a basic ingredient in medicine: physicochemical parameters and characterization

• Gabriel M. Misirli,
• Kishore Sridharan and
• Shirley M. P. Abrantes

Beilstein J. Nanotechnol. 2021, 12, 440–461, doi:10.3762/bjnano.12.36

• human serum albumin (HSA), fibrinogen and immunoglobulin (IgG), metallothionein (MT), and ceruloplasmin (CP), forming a protein corona (PC) during silver homeostasis [121][122]. The PC is a highly dynamic system and its composition dynamically changes over time, undergoing various transformations until

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

• affect the uptake. Once NPs enter biological fluids (blood or culture medium with serum), proteins immediately adsorb onto the surface of the NPs, forming a layer called protein corona (PC). The PC changes the surface composition and structure of NPs, directly influences the cell–NP interactions

• the protein corona in terms of the amount and specificity of proteins adsorbed from the serum, overall affecting the final size of the nanoparticles in the biological fluid [46]. Because the cellular entry mechanism of identical nanoparticles can differ between cancer cells and non-malignant cells [47

Effect of different silica coatings on the toxicity of upconversion nanoparticles on RAW 264.7 macrophage cells

• Cynthia Kembuan,
• Helena Oliveira and
• Christina Graf

Beilstein J. Nanotechnol. 2021, 12, 35–48, doi:10.3762/bjnano.12.3

• -average values of the samples after redispersion in DMEM were lower than in water, except for the samples UC@thin_NH2, UC@thick_RBITC_NH2, and SiO2@RBITC_NH2. The lower Z-average values of these samples may indicate an increased stabilization by a protein corona [52][53][54][55][56]. However, the high

• aggregation of silica nanoparticles that occurred after redispersion in buffered solution and in physiological medium [54]. They reported that various proteins in a medium containing FBS were adsorbed onto the surface of bare SiO2 and amine-functionalized SiO2 nanoparticles, forming a protein corona with a

• new surface charge, which depended on the type of proteins that built the corona. The adsorbed protein corona, consisting of the proteins present in FBS, could increase or reduce the stability of the particles and, consequently, their hydrodynamic diameter [53][54][55][56][57]. The non-functionalized

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

• protein corona forming around them, by investigating the particle–cell interactions or by looking for biomimetic solutions. Blood–brain barrier anatomy. Inspired by [5]. Brain delivery routes. A) Local delivery. Drugs can reach the brain by direct injection through the meninges. B) Intranasal delivery

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

• purpose of investigating the role of surface curvature and chemistry on platelet aggregation, activation and adhesion. Substantial differences were found in the composition of the protein corona depending on the chemical nature of the nanoparticles, while the surface curvature was found to play a minor

• –protein interaction may lead to bridging among particles, thus promoting agglomeration [23]. In the present study, a set of six silica and carbon NPs of known size and morphology was used to evaluate the effect of the size and surface properties on the protein corona composition, platelet activation and

• polystyrene cuvette, at 25 °C. PBS 0.01 M, pH 7.4, Sigma-Aldrich, was used as the diluent in the case of the evaluation of the size after the protein corona formation. Nanoparticle tracking analysis (NTA) An analysis of the size distribution and concentration of CNPs and SNPs were performed by NTA using a

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

• to predict the evolution of their protein corona [60][61][198]. Other studies are trying to understand not only whether certain biomolecules are present on the nanoparticle surface, but also their orientation, which might influence their recognition by cell receptors [17][199]. In order to take into

Using gold nanoparticles to detect single-nucleotide polymorphisms: toward liquid biopsy

• María Sanromán Iglesias and
• Marek Grzelczak

Beilstein J. Nanotechnol. 2020, 11, 263–284, doi:10.3762/bjnano.11.20

• . Specifically, the recently proposed protein corona sensor arrays in which the composition of protein corona reflects the presence of a given cancer enabled new venues in detecting diseases directly from a blood sample [140]. Moreover, the simultaneous detection of genetic mutations and disease-specific

• ]. Several limitations need to be addressed as well. One of the known issues in colloidal biosensing is the spontaneous formation of a protein corona on the surface of the particles in physiological media [146], inhibiting the interaction of the biomarkers with the colloid, thereby altering the sensitivity

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

Bombesin receptor-targeted liposomes for enhanced delivery to lung cancer cells

• Mohammad J. Akbar,
• Pâmela C. Lukasewicz Ferreira,
• Melania Giorgetti,
• Leanne Stokes and
• Christopher J. Morris

Beilstein J. Nanotechnol. 2019, 10, 2553–2562, doi:10.3762/bjnano.10.246

• polydisperse proteins of different sizes [27]. Indeed, the surface properties of various nanoparticles have been shown to change dramatically in the presence of plasma or serum [28] with the establishment of an adsorbed protein corona around the nanoparticle. It is now widely accepted that the particle protein

• corona presents a new biomolecular interface that underpins the dynamic interactions of nanosystems and their biological targets. The presentation of a high affinity GRPR antagonist peptide on the liposomal surface is expected to maintain liposomal cell-binding affinity by virtue of its high affinity for

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) for dual-modality imaging of intracranial glioblastoma via EGFRvIII targeting

• Xianping Liu,
• Chengjuan Du,
• Haichun Li,
• Ting Jiang,
• Zimiao Luo,
• Zhiqing Pang,
• Daoying Geng and
• Jun Zhang

Beilstein J. Nanotechnol. 2019, 10, 1860–1872, doi:10.3762/bjnano.10.181

• proteins, resulting in the formation of protein corona [48][49]. To minimize the adverse effects of the presence of the protein corona in vivo, the surface coating using PEG can endow the NPs with so-called “stealth” properties to reduce the adsorption of high molecular weight proteins, allowing them to

Serum type and concentration both affect the protein-corona composition of PLGA nanoparticles

• Katrin Partikel,
• Robin Korte,
• Dennis Mulac,
• Hans-Ulrich Humpf and
• Klaus Langer

Beilstein J. Nanotechnol. 2019, 10, 1002–1015, doi:10.3762/bjnano.10.101

• /bjnano.10.101 Abstract Background: When nanoparticles (NPs) are applied into a biological fluid, such as blood, proteins bind rapidly to their surface forming a so-called “protein corona”. These proteins are strongly attached to the NP surface and confers them a new biological identity that is crucial

• for the biological response in terms of body biodistribution, cellular uptake, and toxicity. The corona is dynamic in nature and it is well known that the composition varies in dependence of the physicochemical properties of the NPs. In the present study we investigated the protein corona that forms

• assay, zeta potential measurements, and liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS). Additionally, the time-dependent cell interaction of PLGA NPs in the absence or presence of a preformed protein corona was assessed by in vitro incubation experiments with the human liver cancer

Engineering of oriented carbon nanotubes in composite materials

• Razieh Beigmoradi,
• Abdolreza Samimi and
• Davod Mohebbi-Kalhori

Beilstein J. Nanotechnol. 2018, 9, 415–435, doi:10.3762/bjnano.9.41

• the CNT diameter and length are critical parameters in protein corona formation and biocompatibility [11][12]. In another research investigating the effect of aligning CNTs in composite material structures, a remarkable improvement in the electrical properties of CNT composites was observed, as

Methionine-mediated synthesis of magnetic nanoparticles and functionalization with gold quantum dots for theranostic applications

• Arūnas Jagminas,
• Agnė Mikalauskaitė,
• Vitalijus Karabanovas and
• Jūrate Vaičiūnienė

Beilstein J. Nanotechnol. 2017, 8, 1734–1741, doi:10.3762/bjnano.8.174

• have a dramatic effect on the formation of the surface protein corona in the bloodstream that affects CoFe2O4@Met–Au NPs passive targeting and uptake into tumor cells. The elaborated functionalization of magnetic NPs with gold QDs represents a promising multi-task platform for linking magnetic NPs with

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

• amounts of salts, amino acids and proteins. In aqueous media, electrostatic repulsion contributes to particle stabilisation. In presence of salts at neutral pH values, this type of stabilisation might be ineffective. In contrast, the formation of a protein corona at the interface between particle surface

Evaluation of quantum dot conjugated antibodies for immunofluorescent labelling of cellular targets

• Jennifer E. Francis,
• David Mason and
• Raphaël Lévy

Beilstein J. Nanotechnol. 2017, 8, 1238–1249, doi:10.3762/bjnano.8.125

• between Qdots and functional antibodies, the overall surface charge of Qdot-Ab conjugates, and whether there is a presence of a protein corona. The labelling ratio of Qdots to antibodies present within commercially available Qdot-Ab conjugates has been previously evaluated, where the non-specific

• protein adsorption and thus the formation of a protein corona [38]. Qdots with a zwitterionic surface have a zeta potential of near zero, are resistant to non-specific binding onto cells, and have a high colloidal stability [39]. Commercially available Qdot-Abs evaluated in this report were used in fixed

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

• , which could be a desirable event in targeted tumour therapy. The optimal uptake conditions for NPs could depend on the particle size, surface modifications, protein corona, and recipient cell line. Previous studies have suggested the incubation of NIH3T3 mouse fibroblasts with 16 nM QDs for 6 h as the

• varies depending on the cell and particle type. One of the factors affecting uptake is the protein corona that forms around NPs in serum-containing medium. Protein aggregates decrease gold NP uptake depending on size and cell type [41]. In the present study, we analysed the QD uptake pathways under both

• QDs possessing a protein corona are differently recognized by NIH3T3 cells and internalized by different pathways [23], consistent with the data from the present study. Interestingly, MSCs showed more effective internalization of QDs under serum-free conditions, as the protein corona interferes with

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

• dispersion in biological media containing proteins (like RPMI/10% FCS) is much better due to the formation of a protein corona [48][49]. The concentration of the labelled proteins was determined by UV–vis spectroscopy (Table 2). Table 3 gives the quantification data of the functionalized nanoparticles, where

• also influence their uptake [64][65][66][67]. Krais et al. have shown that serum proteins were necessary for cancer cells to take up folic acid-conjugated iron oxide nanoparticles [68]. The nature of the protein corona on the protein-loaded calcium phosphate nanoparticles after immersion in cell

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

• dependent on particle size and the serum content in the culture medium [11][12]. In serum-free conditions the uptake of SiNPs has been determined to be much higher than in the presence of fetal calf serum (FCS), which is attributed to the fact that SiNPs build up a protein corona and tend to agglomerate in

Surface coating affects behavior of metallic nanoparticles in a biological environment

• Darija Domazet Jurašin,
• Marija Ćurlin,
• Ivona Capjak,
• Tea Crnković,
• Marija Lovrić,
• Michal Babič,
• Daniel Horák,
• Ivana Vinković Vrček and
• Srećko Gajović

Beilstein J. Nanotechnol. 2016, 7, 246–262, doi:10.3762/bjnano.7.23

• may serve as desirable barriers preventing NPs from agglomeration in biomedical applications [18]. Moreover, when NPs enter a biological fluid, electrostatic, dispersive, and covalent interactions cause proteins to adsorb on NP surfaces, leading to the formation of a dynamic protein corona [30][36][37

• uptake and toxicity of metallic NPs [41][42], whereas differences in surface coatings influence cytotoxicity and surface charge [43]. However, it is still unclear how different surface coatings affect the interaction of NPs with biological environments and the formation of the protein corona. Because

• evaluation of metallic NPs in biological environments. Effect of albumin on the dispersibility of AgNPs and SPIONs in biological media When suspended in biological fluids, NPs rapidly interact with proteins that form a dynamical layer all over the NP surface, known as a protein corona (PC) [36][37][39

The eNanoMapper database for nanomaterial safety information

• Nina Jeliazkova,
• Charalampos Chomenidis,
• Philip Doganis,
• Bengt Fadeel,
• Roland Grafström,
• Barry Hardy,
• Janna Hastings,
• Markus Hegi,
• Vedrin Jeliazkov,
• Nikolay Kochev,
• Pekka Kohonen,
• Cristian R. Munteanu,
• Haralambos Sarimveis,
• Bart Smeets,
• Pantelis Sopasakis,
• Georgia Tsiliki,
• David Vorgrimmler and
• Egon Willighagen

Beilstein J. Nanotechnol. 2015, 6, 1609–1634, doi:10.3762/bjnano.6.165

• templates (e.g., Protein Corona CSV files or ModNanoTox Excel files), and custom formats, provided by partners (e.g., the NanoWiki RDF dump [27]). ISA-Tab [15] files are converted by compressing the chain of protocols into a single entry, yet retaining all the protocol parameters and recording the material

• allowing parsing of the entire ModNanoTox complex organisation into the internal eNanoMapper data model. Protein Corona The demonstration data set, extracted from [28], focuses on the biological identity of ENMs. The authors used the composition of the protein corona “fingerprint” to predict the cell

• . Among the factors in play in protein corona, biological interaction was chosen to be represented by cell association because of its relevance to biodistribution, inflammatory response potential, and in vivo toxicity. The eNanoMapper prototype described in this paper is able to capture this protein

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

• Hospital of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany 10.3762/bjnano.6.88 Abstract In biological environments, nanoparticles are enshrouded by a layer of biomolecules, predominantly proteins, mediating its subsequent interactions with cells. Detecting this protein corona, understanding its

• formation with regards to nanoparticle (NP) and protein properties, and elucidating its biological implications were central aims of bio-related nano-research throughout the past years. Here, we discuss the mechanistic parameters that are involved in the protein corona formation and the consequences of this

• involvement of Coulomb-type interactions between NPs and charged patches on the protein surface. Moreover, we discuss novel aspects related to the complexity of the protein corona forming under physiological conditions in full serum. Specifically, we address the relation between particle size and corona

Biological responses to nanoscale particles

• Reinhard Zellner

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

• , their surface-active components (i.e., proteins) will adhere to the nanoparticles and form a so-called “protein corona”. As a result, biological systems never come into contact with bare nanoparticles, but rather with their protein-coated analogues. Since this discovery, a large variety of experimental

• preferred as a function of shape, size, and most importantly, surface functionalization and protein corona, could thus far not be established. The SPP1313 research network resulted from an open national call after an intensive evaluation of proposals by an international group of experts. It operated for a

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

• their toxicity is of prime interest in the safety evaluation of NP. Importantly, for a precise understanding of the biological and toxicological effects of complex NP it is important to understand which part of the NP induces the observed effects, e.g., the inorganic core, the ligand shell, the protein

• corona or even the drug or label inside or associated with the particle. Therefore, more sophisticated imaging methods are needed that allow one to distinguish different parts of a NP within tissues or cells. Furthermore, the expertise of specially trained toxicological pathologists is essential in any