Exploring the potential of polymers: advancements in oral nanocarrier technology

• Rousilândia de Araujo Silva,
• Igor Eduardo Silva Arruda,
• Luise Lopes Chaves,
• Mônica Felts de La Roca Soares and
• Jose Lamartine Soares Sobrinho

Beilstein J. Nanotechnol. 2025, 16, 1751–1793, doi:10.3762/bjnano.16.122

• coated pits along the plasma membrane. These pits undergo disassembly via dynamin, leading to the formation of vesicles that are transported to endosomes for subsequent degradation. NPs smaller than 200 nm with a positive surface charge, as well as growth factors and transferrin, are internalized through

Enhancing the therapeutical potential of metalloantibiotics using nano-based delivery systems

• Alejandro Llamedo,
• Marina Cano,
• Raquel G. Soengas and
• Francisco J. García-Alonso

Beilstein J. Nanotechnol. 2025, 16, 1350–1366, doi:10.3762/bjnano.16.98

• complexes. In another example, a nano-based delivery system was developed comprising the zinc–rifampicin complex (Zn-RIF) 16 (Figure 4) encapsulated within transferrin-functionalized silver quantum dots (Zn-RIF-Tf-QDs) [122]. This formulation markedly enhanced antimycobacterial activity, with at least a

Ferroptosis induction by engineered liposomes for enhanced tumor therapy

• Alireza Ghasempour,
• Mohammad Amin Tokallou,
• Mohammad Reza Naderi Allaf,
• Mohsen Moradi,
• Hamideh Dehghan,
• Mahsa Sedighi,
• Mohammad-Ali Shahbazi and
• Fahimeh Lavi Arab

Beilstein J. Nanotechnol. 2025, 16, 1325–1349, doi:10.3762/bjnano.16.97

• increase the activity of the enzyme lipoxygenase, which, as mentioned in the previous section, is associated with ferroptosis [49]. To investigate the role of iron in ferroptosis, we should first familiarize ourselves with its metabolism within the cell. Transferrin is responsible for ferric iron (Fe+3

• ) transportation in the body. Due to the role of this transporter in the supply of iron in the cell, it has recently been introduced as one of the specific markers of ferroptosis [50]. Like transferrin, lactoferrin also plays a role in iron transport [51]. Cells absorb iron-bound transferrin with the help of

• transferrin receptor 1 (TFR1) during receptor-bound endocytosis. In addition to this pathway, iron absorption can also occur with the help of actin filaments, one of the components of the cytoskeleton, via the receptor (TFRC) [36]. The iron required by the cell, in the form of ferrous iron (Fe+2), is produced

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

• , a ligand of transferrin receptor, and NGR peptide, a ligand of CD13 [127]. Dual modification with the peptides yielded the ability to overcome the BBB and target the glioma. In another study, RBC-covered graphene oxide quantum dots (GTDC@M) were investigated regarding the targeted therapy of

Synthetic-polymer-assisted antisense oligonucleotide delivery: targeted approaches for precision disease treatment

• Ana Cubillo Alvarez,
• Dylan Maguire and
• Ruairí P. Brannigan

Beilstein J. Nanotechnol. 2025, 16, 435–463, doi:10.3762/bjnano.16.34

• antitumour activity in xenograft mouse models. Later experiments investigated the effect resulting from the incorporation of targeting agents into the surface of lipid–polycation vectors. For example, Yuan et al. prepared transferrin-conjugated PEI1200–lipid nanoparticles (LPNs), for the targeted delivery of

• G3139 to acute myeloid leukemic cells [113]. Agarose gel electrophoresis retardation essays revealed that both PEI and transferrin were critical to achieve nanocomplexes with long-term stability and optimal cargo protection under physiological conditions. Moreover, LPNs exhibited enhanced cellular

• activity of a series of transferrin-conjugated LPNs with varied physicochemical properties, designed to deliver a phosphorothioate ASO targeting ribonucleotide nuclease R1 [114]. Experimental and in vitro studies indicated that optimal biostability and cytocompatibility were achieved with particles bearing

Polymer lipid hybrid nanoparticles for phytochemical delivery: challenges, progress, and future prospects

• Iqra Rahat,
• Pooja Yadav,
• Aditi Singhal,
• Mohammad Fareed,
• Jaganathan Raja Purushothaman,
• Mohammed Aslam,
• Raju Balaji,
• Sonali Patil-Shinde and
• Md. Rizwanullah

Beilstein J. Nanotechnol. 2024, 15, 1473–1497, doi:10.3762/bjnano.15.118

• specific enzymes can trigger drug release [74]. For instance, Wang et al. fabricated transferrin ligand-decorated redox-sensitive PLHNPs to achieve improved therapeutic efficacy of afatinib against non-small cell lung cancer [70][75]. The complete scheme for the development of ligand-decorated redox

Nanotechnological approaches for efficient N2B delivery: from small-molecule drugs to biopharmaceuticals

• Selin Akpinar Adscheid,
• Akif E. Türeli,
• Nazende Günday-Türeli and
• Marc Schneider

Beilstein J. Nanotechnol. 2024, 15, 1400–1414, doi:10.3762/bjnano.15.113

• conducted for polymeric nanoparticles to understand their role in N2B delivery. For instance, Gabold et al. reported the preparation of protein-loaded chitosan NPs decorated with transferrin as a proof-of-concept study to demonstrate a versatile surface functionalization that can also be suitable for N2B

• delivery. They showed that the transferrin-decorated NPs with the highest amount of targeting ligand exhibited the highest cellular uptake in the RPMI 2650 human epithelium cell line [79]. In another study, the researchers studied the chitosan coating of PLGA NPs regarding the mucosal uptake. Chatzitaki et

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

• comparison of the impact of NP size on the tumor accumulation and retention of actively targeted particles was undertaken by Xu and colleagues [87]. The authors synthesized transferrin-coated iron oxide NPs with core sizes of 3 and 30 nm and assessed their binding to transferrin receptors overexpressed in a

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

• diameter of clathrin-coated invaginations is about 100 nm, and it has a turnover of about 1 min; for a review, see [67]. A commonly used tool to interfere with this process is chlorpromazine, which affects clathrin in some cell types but not in others [68]. When trying to block CME one may use transferrin

• -macroglobulin, EGF, and transferrin, and a concomitant depletion of these receptors at the plasma membrane [46]. One might expect that other receptors that normally recycle after uptake from clathrin-coated pits are also affected in a similar manner, and that NPs targeting such receptors might have a reduced

• membrane tension [69]. Thus, any treatment that affects cell morphology and thus may change membrane tension, could have an effect on actin dependency. In agreement with this is the finding that the insertion of lysolipids into the membrane made transferrin uptake more dependent on actin [70]. Knockdown of

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

• receptor (ER), folate receptors (FRs), human epithelial receptor (HER-2) and transferrin receptors (TfRs) [30][31][32][33][34], has been explored extensively. The selective targeting of these molecular targets via antibody-conjugated NPs provides an efficient platform to accurately deliver the drug cargo

• -containing media, which confirmed protein corona formation. The protein corona establishes a barrier between the ligand and the target, significantly reducing the NP targeting efficiency as compared to bare NPs [79]. Salvati et al. developed transferrin (Tf)-modified fluorescent silica NPs to evaluate the

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

• . Transferrin [1] can be used as a maker for clathrin-mediated endocytosis (CME), bodipy-lactosylceramide (LacCer) can be used for caveolae-mediated endocytosis, and dextran with large molecular masses can be used for macropinocytosis [36]. Moreover, concentration should be optimized (Table 2) and toxicity

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

• achievable utilizing NPs less than 100 nm in diameter. In contrast, active targeting strategies involve functionalizing the NP surface with appropriate ligands specific for receptors overexpressed by the cancer cells (e.g., folic acid and transferrin). The combination of the paracellular gap size resulting

Cyclodextrins as eminent constituents in nanoarchitectonics for drug delivery systems

• Makoto Komiyama

Beilstein J. Nanotechnol. 2023, 14, 218–232, doi:10.3762/bjnano.14.21

• siRNA from the endosome. In another example, a supramolecular nanoparticle was prepared from a linear CyD-based polymer, hydrophilic polyethylene glycol bearing an adamantane at the end, and siRNA [64]. By attaching a human transferrin protein, this composite was steered to target cancer cells to

• transferrin (tumor-targeting protein) which bears poly(ʟ-lysine), mitochondrion-targeting peptide, poly(ethylene glycol), and arylazopyrazole (trans isomer) [89]. Under irradiation with NIR light (808 nm), the photothermal effect disrupted mitochondrial function, leading to inhibition of tumor growth. 6 Some

Systematic studies into uniform synthetic protein nanoparticles

• Nahal Habibi,
• Ava Mauser,
• Jeffery E. Raymond and
• Joerg Lahann

Beilstein J. Nanotechnol. 2022, 13, 274–283, doi:10.3762/bjnano.13.22

• this knowledge gap by evaluating formulation trends in SPNPs prepared by EHD jetting based on a series of carrier proteins and protein blends (hemoglobin, transferrin, mucin, or insulin). In general, blended SPNPs presented uniform populations with minimum diameters between 43 and 65 nm. Size

• proteins with specific biological functions, such as transferrin, insulin, albumin, mucin, or hemoglobin, may represent powerful candidates as next-generation biologics. The EHD jetting process is influenced by a number of governing principles, such as viscosity and dielectric constant of the premixture

• Discussion Single-protein SPNPs A range of SPNP formulations were prepared via EHD jetting from hemoglobin (HEM), transferrin (TF), mucin (MUC), insulin (INS), and human serum albumin (HSA) (Figure 1a). Generally, dilute solutions of a protein at 10% (w/v) in a 9:1 (v/v) mixture of water and ethanol were

Use of nanosystems to improve the anticancer effects of curcumin

• Andrea M. Araya-Sibaja,
• Norma J. Salazar-López,
• Krissia Wilhelm Romero,
• José R. Vega-Baudrit,
• J. Abraham Domínguez-Avila,
• Carlos A. Velázquez Contreras,
• Ramón E. Robles-Zepeda,
• Mirtha Navarro-Hoyos and
• Gustavo A. González-Aguilar

Beilstein J. Nanotechnol. 2021, 12, 1047–1062, doi:10.3762/bjnano.12.78

• shown to increase the antiproliferative effect (IC50 12.4 µM) of CUR, as compared to the free molecule (IC50 17.2 µM) within the assayed range (5–40 µM) [132]. Cui et al. [134] reported the use of CUR-loaded MNP to achieve active targeting in conjunction with transferrin receptor binding peptide T7

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

The impact of molecular tumor profiling on the design strategies for targeting myeloid leukemia and EGFR/CD44-positive solid tumors

• Nikola Geskovski,
• Nadica Matevska-Geshkovska,
• Simona Dimchevska Sazdovska,
• Marija Glavas Dodov,
• Kristina Mladenovska and
• Katerina Goracinova

Beilstein J. Nanotechnol. 2021, 12, 375–401, doi:10.3762/bjnano.12.31

• , and regardless of the steric barrier, somehow managed to interact with the sinusoidal endothelial cells of the BM. One possible explanation is that the recognition may be mediated by a plasma component (such as erythropoietin, transferrin, or transcobalamin) or an endothelial factor that specifically

• arrest, demonstrating a sensitiveness of the cells to nilotinib that is attributable to IM. Mendonca and co-workers worked on developing a targeted NDDS for а combination of siRNA and TKI in CML treatment [63]. The authors developed sterically stabilized liposomes decorated with transferrin for co

• reflected on the evaluated IC50 values of IM on different cell lines. Additionally, the comparative analysis of the IC50 values on different cell lines revealed that the transferrin receptor expression and the cellular levels of BCR-ABL mRNA affected the efficacy of the formulation. The cell lines with

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

• into A549 cells via CavME or another CME-independent route of endocytosis. Surprisingly, the inhibition of CME by CPZ and MDC resulted in a significantly increased uptake of PEG-SO-MNPs compared to control cells. Positive controls A fluorescently labeled Alexa Fluor 594–transferrin conjugate (Tr

• transferrin (Tr) internalization than MDC in A549 cells. Caveolae and lipid raft internalizations are known to be inhibited by N, F, and MBCD through depletion of cholesterol from the cell membrane [51]. While F and N were described to be very specific inhibitors of caveolin-mediated endocytosis (CavME

• ). Single-cell clones were selected and amplified by dilution cloning in 6-well plates. Immunofluorescence staining Cells were grown on glass coverslips in 48-well plates overnight before incubation with Alexa Fluor 594–Transferrin conjugate (25 µg/mL) or cholera Toxin B subunit–FITC conjugate (5 mg/mL) at

Applications of superparamagnetic iron oxide nanoparticles in drug and therapeutic delivery, and biotechnological advancements

• Maria Suciu,
• Corina M. Ionescu,
• Alexandra Ciorita,
• Septimiu C. Tripon,
• Dragos Nica,
• Hani Al-Salami and
• Lucian Barbu-Tudoran

Beilstein J. Nanotechnol. 2020, 11, 1092–1109, doi:10.3762/bjnano.11.94

• pool (ferritin and transferrin) for normal metabolic activities [20]. In localized hyperthermia, SPIONs generate heat by constantly aligning to an alternating magnetic field. This heat is rapidly transferred to the surrounding cancerous tissue in which proteins denature and, consequently, cells become

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

• receptors found on the luminal side of the BBB are transferrin receptor (TfR), insulin and insulin-like growth factor receptor, low-density lipoprotein receptor (LDLR), low-density lipoprotein receptor-related protein 1 and 2 (LRP1 and LRP2), scavenger receptor class B type I (SR-B1), leptin receptor and

• LRP1, also enables BBB crossing. Another extensively studied RMT pathway is through transferrin and lactoferrin receptors by conjugating nanoparticles with their respective ligands, transferrin and lactoferrin [72][73][74][87][88]. However, these nanoparticles have to face competition with the

• endogenous ligands of these receptors. This problem can be avoided by using antibodies against transferrin receptors, i.e., OX26, which bind to another binding site of the receptor [74][80][81][82][83]. However, it has been shown that OX26 is mostly associated with brain capillaries through the brain

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

• active targeting [9][10][11][12]. These surface-functionalized nanomaterials should be internalized preferentially by cells that overexpress the targeted receptors. Examples of targeting moieties often exploited in nanomedicine are transferrin and folate, which target tumour cells overexpressing the

• biomolecules among which low density lipoprotein for cholesterol uptake and transferrin for iron uptake. After binding of the ligand to its receptor, clathrin, the main actor in CME, is recruited at the cell membrane together with several other proteins and assembles around the forming vesicle to form a

• and transferrin can be used as markers for clathrin-mediated endocytosis [205][206], dextran as a fluid phase marker for phagocytosis and for the CLEE/GEEC pathway [193], and LacCer (C5-lactosylceramide) for cholesterol-dependent uptake [133][207]. However, while cholera toxin and SV40 were previously

Internalization mechanisms of cell-penetrating peptides

• Ivana Ruseska and
• Andreas Zimmer

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

• occurs in all mammalian cells and supports the continuous uptake of essential nutrients such as LDL particles, which carry cholesterol to cells and bind to the LDL receptor (LDLR), and iron-laden transferrin (Tfn) that binds to Tfn receptors (TfnR) [52]. It is a crucial process throughout the life of an

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

• , leading to accumulation of nanocarriers in the tumour. A diversity of targeting ligands has been explored, including antibodies, proteins, peptides and aptamers. Targeted nanoparticles such as HER2-targeted MM-302 [14], transferrin receptor-targeted CALAA-01 [15], and prostate-specific membrane antigen

• . PMT settings were medium and 3 reads performed per well. Data is represented as 340/380 ratio using zero baseline for normalisation. Cell proliferation assay The proliferation of NCI-H345 and NCI-H82 cells in the presence or absence of Tyr4-Bn and cystabn was studied in selenium–insulin–transferrin

• (SIT) medium comprising 30 nM sodium selenite, 5 µg/mL human insulin, 10 μg/mL human transferrin and 2 mM ʟ-glutamine in RPMI-1640 media. The cells were seeded in 96 well plates overnight at a density of 30,000 cells per well. The cells were then treated with 100 or 500 nM Tyr4-Bn or cystabn and for 5

Small protein sequences can induce cellular uptake of complex nanohybrids

• Jan-Philip Merkl,
• Malak Safi,
• Christian Schmidtke,
• Fadi Aldeek,
• Johannes Ostermann,
• Tatiana Domitrovic,
• Sebastian Gärtner,
• John E. Johnson,
• Horst Weller and
• Hedi Mattoussi

Beilstein J. Nanotechnol. 2019, 10, 2477–2482, doi:10.3762/bjnano.10.238

• various proteins, and among them the human transferrin protein was found to induce the highest intracellular uptake following 24 h incubation of these hybrids with cell cultures [5]. In the second, functional colloidal superstructures assembled using DNA linkers elicited a reduction in the response of

• ), and QDs in yellow. The images clearly indicate that QDs and Cy5-transferrin do not co-localize. In addition, the dark signals observed in bright field mode, coincide with the yellow fluorescence emitted when we switch to fluorescence mode. This indicates that these spot signals are assemblies of

• a region, where the QD fluorescence staining is close to the Cy5-transferrin associated with the endosomal marker (Figure 2C). The two stainings corresponding to the nanohybrids and Cy-5-transferrin do not share the same compartments. Clearly, these findings combined show that the nanocomposites

Design of a nanostructured mucoadhesive system containing curcumin for buccal application: from physicochemical to biological aspects

• Sabrina Barbosa de Souza Ferreira,
• Gustavo Braga,
• Évelin Lemos Oliveira,
• Jéssica Bassi da Silva,
• Hélen Cássia Rosseto,
• Lidiane Vizioli de Castro Hoshino,
• Mauro Luciano Baesso,
• Wilker Caetano,
• Craig Murdoch,
• Helen Elizabeth Colley and
• Marcos Luciano Bruschi

Beilstein J. Nanotechnol. 2019, 10, 2304–2328, doi:10.3762/bjnano.10.222