Safe and sustainable by design with ML/AI: A transformative approach to advancing nanotechnology

• Georgia Melagraki

Beilstein J. Nanotechnol. 2026, 17, 176–185, doi:10.3762/bjnano.17.11

• interpolation from limited experimental datasets [57]. Given that protein corona formation [58] can drastically alter the biodistribution and immunological profile of a nanoparticle, digital twins help pinpoint safer design parameters – such as surface coatings or particle size modifications – which improve

From shield to spear: Charge-reversible nanocarriers in overcoming cancer therapy barriers

• Madhuri Yeduvaka,
• Pooja Mittal,
• Ameer Boyalakuntla,
• Usman Bee Shaik,
• Himanshu Sharma,
• Thakur Gurjeet Singh,
• Siva Nageswara Rao Gajula and
• Lakshmi Vineela Nalla

Beilstein J. Nanotechnol. 2026, 17, 159–175, doi:10.3762/bjnano.17.10

• also induce cytotoxicity and rapid clearance by the mononuclear phagocyte system [18]. Moreover, surface charge influences aggregation behaviour, colloidal stability, and protein corona formation, directly impacting the therapeutic efficacy of nanocarriers. Optimising surface charge is essential for

Influence of surface characteristics on the in vitro stability and cell uptake of nanoliposomes for brain delivery

• Dushko Shalabalija,
• Ljubica Mihailova,
• Nikola Geskovski,
• Andreas Zimmer,
• Otmar Geiss,
• Sabrina Gioria,
• Diletta Scaccabarozzi and
• Marija Glavas Dodov

Beilstein J. Nanotechnol. 2026, 17, 139–158, doi:10.3762/bjnano.17.9

• NLs interact with biomolecules, thus forming a protein corona (PC), altering functional proteins, and engaging in redox reactions with reactive species [6]. These interactions can affect the functionality, biodistribution, targeting, and cell internalization of NLs. Serum components can disrupt the

• ) after their incubation in cell culture medium with and without serum for a period of 1 and 4 h. It is well known that PEGylation plays a critical role in modulating the formation and composition of the protein corona on nanoparticles by introducing a steric barrier that reduces and selectively alters

• protein adsorption. The extent of this modulation strongly depends on both the PEG grafting density and the molecular weight of the PEG chains. Namely, the incorporation of 50 mg of DSPE-mPEG2000 serves to introduce a PEGylated surface that effectively modulates protein corona formation upon exposure to

Development and in vitro evaluation of liposomes and immunoliposomes containing 5-fluorouracil and R-phycoerythrin as a potential phototheranostic system for colorectal cancer

• Raissa Rodrigues Camelo,
• Vivianne Cortez Sombra Vandesmet,
• Octavio Vital Baccallini,
• José de Brito Vieira Neto,
• Thais da Silva Moreira,
• Luzia Kalyne Almeida Moreira Leal,
• Claudia Pessoa,
• Daniel Giuliano Cerri,
• Maria Vitória Lopes Badra Bentley,
• Josimar O. Eloy,
• Ivanildo José da Silva Júnior and
• Raquel Petrilli

Beilstein J. Nanotechnol. 2026, 17, 97–121, doi:10.3762/bjnano.17.7

• protein corona formation under physiological conditions [63]. These findings highlight the importance of surface characterization by AFM in the development and optimization of nanoparticles. 3.4 Fourier-transform infrared spectroscopy assays The FTIR spectra obtained for the formulations showed the

• polymer is known to reduce protein corona formation and confer greater stability in biological media [69][70]. In immunoliposomes, a tendency for size and PDI to increase after 24–48 h of incubation was observed, suggesting possible adsorption of serum proteins and/or reorganization of antibody chains on

Toward clinical translation of carbon nanomaterials in anticancer drug delivery: the need for standardisation

• Michał Bartkowski,
• Francesco Calzaferri and
• Silvia Giordani

Beilstein J. Nanotechnol. 2025, 16, 2092–2104, doi:10.3762/bjnano.16.144

• tend to evade renal filtration due to the formation of a protein corona that effectively increases their hydrodynamic size [38]. Beyond renal clearance, particle size also critically influences toxicity, metabolic fate, tumour targeting, protein interactions, and hepatic processing. Additional

PEGylated lipids in lipid nanoparticle delivery dynamics and therapeutic innovation

• Peiyang Gao

Beilstein J. Nanotechnol. 2025, 16, 1914–1930, doi:10.3762/bjnano.16.133

• chains arrange on the nanoparticle surface and the potential impacts on LNPs’ physicochemical properties by varying surface PEG density or PEG chemistry. Subsequently, PEG conformations are discussed in terms of their modulation of protein corona formation, cellular uptake, and immunogenic responses

• properties of LNPs including particle size, surface charge, and encapsulation efficiency. Subsequent sections explore the roles of PEG lipids in modulating protein corona formation and cellular uptake. The latter parts highlight the potential of functionalized PEG lipids for targeted delivery and the

• adsorb onto the nanoparticle surfaces to form a “corona” [21]. This dynamic layer, often called the biomolecular or protein corona, can significantly influence the biological identity and behavior of nanoparticles [22]. Among the factors shaping corona formation, the presence of a PEG layer on the outer

Better together: biomimetic nanomedicines for high performance tumor therapy

• Imran Shair Mohammad,
• Gizem Kursunluoglu,
• Anup Kumar Patel,
• Hafiz Muhammad Ishaq,
• Cansu Umran Tunc,
• Dilek Kanarya,
• Mubashar Rehman,
• Omer Aydin and
• Yin Lifang

Beilstein J. Nanotechnol. 2025, 16, 1246–1276, doi:10.3762/bjnano.16.92

• –protein binding in vivo, nanoparticles can adsorb plasma proteins at their surface in blood circulation and form a corona, which can alter their biodistribution, cell uptake, and intracellular degradation [90]. Thus, as the protein corona increases, albumin proteins affect nanoparticle fate in vivo. As

Serum heat inactivation diminishes ApoE-mediated uptake of D-Lin-MC3-DMA lipid nanoparticles

• Demian van Straten,
• Luuk van de Schepop,
• Rowan Frunt,
• Pieter Vader and
• Raymond M. Schiffelers

Beilstein J. Nanotechnol. 2025, 16, 740–748, doi:10.3762/bjnano.16.57

• Demian van Straten Luuk van de Schepop Rowan Frunt Pieter Vader Raymond M. Schiffelers CDL Research, University Medical Center Utrecht, Utrecht, The Netherlands 10.3762/bjnano.16.57 Abstract Nanoparticles play a crucial role in drug delivery research. The protein corona that develops on the

• surface of nanoparticles after administration has garnered substantial attention due to the significant effects it has on their performance. Lipid nanoparticles (LNPs) depend on protein corona formation to mediate their targeting. Such protein–nanoparticle interactions are often initially studied using in

• performed to prevent complement system activation. However, the effect of this process on protein corona formation and, in turn, LNP functionality is unclear. Here, we investigated the effects of serum heat inactivation on protein corona formation on LNPs containing D-lin-MC3-DMA (MC3) or C12-200 (C12

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