Nanocarriers and macrophage interaction: from a potential hurdle to an alternative therapeutic strategy

• Naths Grazia Sukubo,
• Paolo Bigini and
• Annalisa Morelli

Beilstein J. Nanotechnol. 2025, 16, 97–118, doi:10.3762/bjnano.16.10

• opsonization in the bloodstream, mediated by opsonins that recognize plasma proteins (serum albumin, apolipoproteins, complement components, and immunoglobulins) adsorbed onto the surface of circulating NPs. This forms the so-called “protein corona” (PC), a layer of more than 300 proteins that effectively

Instance maps as an organising concept for complex experimental workflows as demonstrated for (nano)material safety research

• Benjamin Punz,
• Maja Brajnik,
• Joh Dokler,
• Jaleesia D. Amos,
• Litty Johnson,
• Katie Reilly,
• Anastasios G. Papadiamantis,
• Amaia Green Etxabe,
• Lee Walker,
• Diego S. T. Martinez,
• Steffi Friedrichs,
• Klaus M. Weltring,
• Nazende Günday-Türeli,
• Claus Svendsen,
• Christine Ogilvie Hendren,
• Mark R. Wiesner,
• Martin Himly,
• Iseult Lynch and
• Thomas E. Exner

Beilstein J. Nanotechnol. 2025, 16, 57–77, doi:10.3762/bjnano.16.7

• functionalised SiO2 nanomaterials under varying conditions. They also compared artificial and real allergen mixtures by applying genuine detection assays suitable for allergenic molecules in vitro and assessed two recently developed in silico protein corona prediction tools regarding the results from

Attempts to preserve and visualize protein corona on the surface of biological nanoparticles in blood serum using photomodification

• Julia E. Poletaeva,
• Anastasiya V. Tupitsyna,
• Alina E. Grigor’eva,
• Ilya S. Dovydenko and
• Elena I. Ryabchikova

Beilstein J. Nanotechnol. 2024, 15, 1654–1666, doi:10.3762/bjnano.15.130

• protein corona is present on any nanoparticle (NP) entering biological fluids; however, the existence of a natural protein corona on natural NPs has not been experimentally confirmed. We used our previously developed photomodification method to fix the natural corona on “biological nanoparticles” (bio-NPs

• results showed that a protein corona is present on extracellular vesicles and lipoproteins isolated by UC. The isolation of bio-NPs through sucrose gradient or cushion did not preserve the protein corona. At the same time, we observed signs of a negative effect of the sucrose gradient on bio-NPs of intact

• and photomodified serum; when isolating these particles on a sucrose cushion, no negative effects were observed. We believe that the data we present will be useful to researchers using sucrose solutions to isolate bio-NPs and working on the properties of the protein corona. In this work, we have

Dual-functionalized architecture enables stable and tumor cell-specific SiO₂NPs in complex biological fluids

• Iris Renata Sousa Ribeiro,
• Raquel Frenedoso da Silva,
• Romênia Ramos Domingues,
• Adriana Franco Paes Leme and
• Mateus Borba Cardoso

Beilstein J. Nanotechnol. 2024, 15, 1238–1252, doi:10.3762/bjnano.15.100

• -depth studies in complex environments to evaluate nanoparticle stability, protein corona formation, hemolytic activity, and targeting capabilities. To address this issue, fluorescent silica nanoparticles (SiO2NPs) are here functionalized with zwitterionic (kinetic stabilizer) and folate groups

• biological identity of these particles, impairing their therapeutic efficiency [12][13][14][15]. Proteins and other biomolecules can be adsorbed on the surface of NPs (protein corona formation), masking their original functionality and hiding their target ability [16][17][18]. Protein corona can further lead

• and (ii) targeting peptide for targeted delivery aimed at increasing efficiency against cancer. Although valuable, these systems have not been able to provide reduced protein corona formation and targeting ability, or they have not been scrutinized in complex biological environments. In fact, there is

Realizing active targeting in cancer nanomedicine with ultrasmall nanoparticles

• André F. Lima,
• Giselle Z. Justo and
• Alioscka A. Sousa

Beilstein J. Nanotechnol. 2024, 15, 1208–1226, doi:10.3762/bjnano.15.98

• globular proteins, usNPs exhibit unique physicochemical properties and physiological behavior distinct from larger particles, including lack of protein corona formation, efficient renal clearance, and reduced recognition and sequestration by the reticuloendothelial system. In cancer treatment, usNPs

• reliance on passive targeting, the more complex designs of targeted NPs, the potential for attached functional ligands to increase phagocytic capture and shorten blood circulation time, and the formation of a protein corona that may block the targeting ligand on the particle surface [15][16][17]. Over the

• , indicating the formation of a “permanently” bound (hard) protein corona. Moreover, given the appropriate combination of size and surface chemistry, nonspecific interactions between usNPs and proteins can be virtually eliminated (Figure 2C). Notably, achieving highly stable and “stealth” usNPs is feasible

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

• (PEG) chains (e.g., density and chain lengths) and how these chains affect the binding of proteins to the NPs. The protein corona most often contains proteins involved in complement activation, macrophage uptake, lipid metabolism, and blood coagulation [82][83][84][85]. A challenge regarding the

• importance of such studies is that in vitro studies using mice plasma was reported to give a different protein corona than that obtained in vivo in mice [86]. Also, in vitro studies performed in the presence of various serum concentrations revealed different types of protein corona and endocytic uptake [87

Identification of structural features of surface modifiers in engineered nanostructured metal oxides regarding cell uptake through ML-based classification

• Indrasis Dasgupta,
• Totan Das,
• Biplab Das and
• Shovanlal Gayen

Beilstein J. Nanotechnol. 2024, 15, 909–924, doi:10.3762/bjnano.15.75

• “protein corona”, which dictates the biological characteristics of the nanoparticles [10][11]. The composition of this corona is variable and relies on the concentrations and affinities of its different components to the nanoparticle surface. Cellular uptake of NPs happens through receptor-mediated active

Exploring the relationships between physiochemical properties of nanoparticles and cell damage to combat cancer growth using simple periodic table-based descriptors

• Joyita Roy and
• Kunal Roy

Beilstein J. Nanotechnol. 2024, 15, 297–309, doi:10.3762/bjnano.15.27

• protein corona. The formation of a protein corona on the surface of NPs, which influences the interaction with cell membranes or proteins, is also associated with zeta potential and surface charge. Very limited studies have reported the influence of zeta potential, surface charge, hydrophobicity, and

Multiscale modelling of biomolecular corona formation on metallic surfaces

• Parinaz Mosaddeghi Amini,
• Ian Rouse,
• Julia Subbotina and
• Vladimir Lobaskin

Beilstein J. Nanotechnol. 2024, 15, 215–229, doi:10.3762/bjnano.15.21

• protein corona composition in the deposited milk layer on aluminum surfaces. We consider a simplified model of milk, which is composed of the six most abundant milk proteins found in natural cow milk and lactose, which is the most abundant sugar found in dairy. Through our study, we ranked selected

• provide valuable insights into the mechanisms of lactose and protein deposition on aluminum surfaces, which can aid in the general understanding of protein corona formation. Keywords: all atomistic; aluminum; bionano interface; coarse grained model; lactose; milk protein; multiscale modelling; protein

• the mechanisms underlying the formation of NP protein corona, a complex layer of biomolecules that surrounds NPs upon their exposure to biological fluids [19][20]. It is widely recognized that composition and configuration of the protein corona play a crucial role in determining the biochemical

Recognition mechanisms of hemoglobin particles by monocytes – CD163 may just be one

• Jonathan-Gabriel Nimz,
• Pichayut Rerkshanandana,
• Chiraphat Kloypan,
• Ulrich Kalus,
• Saranya Chaiwaree,
• Axel Pruß,
• Radostina Georgieva,
• Yu Xiong and
• Hans Bäumler

Beilstein J. Nanotechnol. 2023, 14, 1028–1040, doi:10.3762/bjnano.14.85

• might not be their Hb content. In their work from 2013, Yan et al. [40] showed how the formation of a protein corona influences particle–cell interactions. Especially bovine serum albumin (BSA) showed an ambivalent effect. On the one hand, the corona, which consisted mainly of BSA, reduced the direct

Antibody-conjugated nanoparticles for target-specific drug delivery of chemotherapeutics

• Mamta Kumari,
• Amitabha Acharya and
• Praveen Thaggikuppe Krishnamurthy

Beilstein J. Nanotechnol. 2023, 14, 912–926, doi:10.3762/bjnano.14.75

• chemotherapeutic agent in a controlled manner. Appropriately designed and synthesized ACNPs are essential to fully realize their therapeutic benefits. In blood stream, ACNPs instantly interact with biological molecules, and a protein corona is formed. Protein corona formation triggers an immune response and

• affects the targeting ability of the nanoformulation. In this review, we provide recent findings to highlight several antibody conjugation methods such as adsorption, covalent conjugation, and biotin–avidin interaction. This review also provides an overview of the many effects of the protein corona and

• ), which eventually decrease the number of NPs at the target site [14]. In blood stream, proteins get adsorbed onto the NPs and form a protein corona. The proteins from the biological environment produce a screening effect, which affects the targeting ability of the NPs [15][16]. Protein corona formation

The steep road to nonviral nanomedicines: Frequent challenges and culprits in designing nanoparticles for gene therapy

• Yao Yao,
• Yeongun Ko,
• Grant Grasman,
• Jeffery E. Raymond and
• Joerg Lahann

Beilstein J. Nanotechnol. 2023, 14, 351–361, doi:10.3762/bjnano.14.30

• be reached, the identification of structure–function and material–biological relations of NPs could be dramatically accelerated. Prevalence of reporting imaging and (or) flow cytometry techniques, protein corona, 3D cell culture model(s), and serum content during nanoparticle incubation with cells in

• investigating NP cellular uptake and (or) transfection. (c) 5-year prevalence of describing or characterizing protein corona in the manuscript. (d) 5-year prevalence of employing 3D cell culture models (e.g., spheroids or organoids). (e) Comparisons of serum content used during nanoparticle incubation with

Polymer nanoparticles from low-energy nanoemulsions for biomedical applications

• Santiago Grijalvo and
• Carlos Rodriguez-Abreu

Beilstein J. Nanotechnol. 2023, 14, 339–350, doi:10.3762/bjnano.14.29

• encapsulated in PLGA nanoparticles derived from PIC nanoemulsions [63]. These antioxidant-loaded nanoparticles feature hydrodynamic sizes between 71 and 160 nm and encapsulation efficiencies higher than 64%. The colloidal stability of the nanoparticle dispersions was not significantly affected by protein

• corona formation (upon incubation in FBS). The nanoparticles showed low cytotoxicity for SH-SY5Y cells (viabilities of ca. 100% for nanoparticle concentrations equal or lower than 0.23 mg/mL), high cellular uptake (in SH-SY5Y cells), and dose-dependent antioxidant activity. The properties of the PIC

Overview of mechanism and consequences of endothelial leakiness caused by metal and polymeric nanoparticles

• Magdalena Lasak and
• Karol Ciepluch

Beilstein J. Nanotechnol. 2023, 14, 329–338, doi:10.3762/bjnano.14.28

• nutrient molecules to NPs could change the toxicity of NPs (NP protein corona), and the physiological conditions, such as blood flow and physiological stretch, will also play a role [37][38][39]. NanoEL mechanism Adherens junctions between endothelial cells are maintained by a complex set of proteins

Recent progress in cancer cell membrane-based nanoparticles for biomedical applications

• Qixiong Lin,
• Yueyou Peng,
• Yanyan Wen,
• Xiaoqiong Li,
• Donglian Du,
• Weibin Dai,
• Wei Tian and
• Yanfeng Meng

Beilstein J. Nanotechnol. 2023, 14, 262–279, doi:10.3762/bjnano.14.24

• system (RES) or the mononuclear phagocytosis system (MPS) [4]. The subsequent rapid clearance from blood circulation by the liver and kidneys results in insufficient drug accumulation in the target tissue [5]. In addition, NPs can interact with proteins to form a protein corona, which affects the

• intended function of the NPs, resulting in changes of biological behavior and loss of function [6][7]. Moreover, the protein corona can accelerate RES/MPS uptake and interfere with the targeting ability of NPs [8]. The biomimetic technique of cell membrane coating, which employs naturally cell-derived

Engineered titania nanomaterials in advanced clinical applications

• Padmavati Sahare,
• Paulina Govea Alvarez,
• Juan Manual Sanchez Yanez,
• Gabriel Luna-Bárcenas,
• Samik Chakraborty,
• Sujay Paul and
• Miriam Estevez

Beilstein J. Nanotechnol. 2022, 13, 201–218, doi:10.3762/bjnano.13.15

• excretion [33]. When a TiO2 nanomaterial circulates through the body, certain biomolecules (such as proteins, phospholipids, or DNA contained in biological fluids or present in living cells) get adsorbed onto the surface of it very quickly, which is termed as “protein corona (PC)” formation. This protein

• corona alters the surface properties and transforms the physical, chemical, and biological characteristics of the nanomaterial. The types and amounts of adsorbed proteins are influenced by certain physiochemical qualities of the nanomaterial, such as the size, shape, charge as well as topography

Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles

• Sadaf Mushtaq,
• Khuram Shahzad,
• Tariq Saeed,
• Anwar Ul-Hamid,
• Bilal Haider Abbasi,
• Nafees Ahmad,
• Waqas Khalid,
• Muhammad Atif,
• Zulqurnain Ali and
• Rashda Abbasi

Beilstein J. Nanotechnol. 2021, 12, 1339–1364, doi:10.3762/bjnano.12.99

• potential values is the interaction between NPs and serum proteins present in DMEM [30]. In cell culture media, NPs agglomerate with serum proteins and are therefore recruited in cells via the protein corona effect, which increases the bioavailability of NPs by many folds [31]. PMA-coated samples have a

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