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

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

• acid [19], transferrin [20] or sugars [21]. But their number is significantly higher in tumoral than in healthy cells due to their stronger nutrient demand. Thus, this receptor overexpression can be exploited for the selective delivery of therapeutic drugs to tumoral cells. Another possibility consists

Green synthesis of fluorescent carbon dots from spices for in vitro imaging and tumour cell growth inhibition

• Nagamalai Vasimalai,
• Vânia Vilas-Boas,
• Juan Gallo,
• María de Fátima Cerqueira,
• Mario Menéndez-Miranda,
• José Manuel Costa-Fernández,
• Lorena Diéguez,
• Begoña Espiña and
• María Teresa Fernández-Argüelles

Beilstein J. Nanotechnol. 2018, 9, 530–544, doi:10.3762/bjnano.9.51

• , antibiotic mixture of penicillin/streptomycin (10,000 U·mL−1/10,000 μg·mL−1), fungizone (250 μg·mL−1), human transferrin (4 mg·mL−1) and phosphate buffered saline solution (1× PBS) were obtained from GIBCO Invitrogen (Barcelona, Spain). Fetal bovine serum (FBS) was obtained from HyClone GE Healthcare (United

• set at 200 °C, and the collision cell energy between 17.5 and 52.5 eV. Cell culture HK-2 cells were grown in DMEM/F12 medium supplemented with 10% FBS, 100 U·mL−1 penicillin/100 μg·mL−1 streptomycin, 2.5 μg·mL−1 fungizone, and 5 μg·mL−1 human transferrin. LN-229 cells were maintained in DMEM high

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

• inhibitor MDC. Inhibition of this pathway was also reported for the Fe-binding protein transferrin, whereas the uptake of non-biological (nano)particles such as polystyrene beads was not blocked [35]. However, the pathway was not exclusively clathrin-mediated because evidence of uptake is observed

Comparison of the interactions of daunorubicin in a free form and attached to single-walled carbon nanotubes with model lipid membranes

• Dorota Matyszewska

Beilstein J. Nanotechnol. 2016, 7, 524–532, doi:10.3762/bjnano.7.46

• between targeting agents and their receptors, such as for example folates and transferrin [7][8]. Additionally, liposomes are also prepared in such a way that simultaneous loading of two drugs into a liposome in order to improve the efficiency of the treatment is possible [9]. Dual drug loading is also

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

• longer circulation times in the blood as well as altered bio-distribution upon injection in mice [155]. Attempts were also made to coat NPs by specific proteins. For example, transferrin, well known to be internalized via its cognate receptor, was used to create a protein corona and study its effect on

• the polymer shell), by live HeLa cells in the presence or absence of human transferrin (TF) and human serum albumin (HSA) in phosphate-buffered saline (PBS) medium. They studied the uptake of the NPs by quantitative confocal fluorescence microscopy. For comparison, they also studied the cellular

• uptake of fluorescently labeled (ca. 1:1 ratio) transferrin and HSA molecules. Whilst transferrin was endocytosed in significant amounts, HSA was barely internalized by HeLa cells under otherwise identical conditions. In contrast, the uncoated NPs were taken up in large amounts, whereas the presence of