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

• of the specific nature of the targeting antibody. ACNPs are expected to accumulate at the target site and to improve the tumor uptake. ACNPs receptor binding efficacies were determined using in vitro studies including cellular uptake and internalization studies [71]. Multivalent effect of antibody

• the receptor-mediated uptake and internalization of NPs in A549 cells. They clearly indicated a significant disparity between in vivo and in vitro outcomes of NP targeting efficacy in the presence of a protein corona [80]. Su et al. reported that protein corona formation alters the active and passive

• the effect of this protein corona. They observed a higher internalization of BLf-AgNPs than of bare AgNPs, which indicates that the protein corona improved the intracellular efficiency of the NPs. Moreover, the BLf corona also increased the bioavailability of the NPs in THP1 cells and resulted in

Green SPIONs as a novel highly selective treatment for leishmaniasis: an in vitro study against Leishmania amazonensis intracellular amastigotes

• Brunno R. F. Verçoza,
• Robson R. Bernardo,
• Luiz Augusto S. de Oliveira and
• Juliany C. F. Rodrigues

Beilstein J. Nanotechnol. 2023, 14, 893–903, doi:10.3762/bjnano.14.73

• internalization of the SPIONs. First, promastigotes were treated with 100 µg/mL of SPIONs for 24 h (Figure 3A–C). TEM images confirmed the presence of SPION aggregates randomly distributed throughout the cytoplasm of the promastigotes (Figure 3A–C, arrowheads). The images suggest that these aggregates have

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

• Need for Multimodal Characterization of Nanoparticles The methods chosen to investigate NP uptake and transfection can be biased towards particular properties and may provide limited insights into the efficiency of NP internalization and efficacy. Typically, cellular uptake and transfection efficiency

• ) [16]. Unfortunately, confocal imaging is limited by relatively low throughput (even with automation) and can be ambiguous when determining internalization within 500 nm of the cell membrane [17]. However, widefield fluorescence microscopy is still widely used when it comes to observing the expression

• papers, Figure 1b). Despite the robust data it can provide, flow cytometry counts the total number of cells associated with NPs and cannot distinguish internalized cargo from surface-bound NPs [1][17]. To precisely quantify internalization, a secondary method is required that can differentiate between

Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

• Filip Gorachinov,
• Fatima Mraiche,
• Diala Alhaj Moustafa,
• Ola Hishari,
• Yomna Ismail,
• Jensa Joseph,
• Maja Simonoska Crcarevska,
• Marija Glavas Dodov,
• Nikola Geskovski and
• Katerina Goracinova

Beilstein J. Nanotechnol. 2023, 14, 240–261, doi:10.3762/bjnano.14.23

• intracellular internalization, and bring advantages over conventional nanocarriers. Keywords: co-delivery nanoparticles; combinatorial therapy; EGFR TKI resistance; non-small cell lung cancer (NSCLC); overcoming and preventing resistance; Introduction Among the malignant diseases, lung cancer takes the lead

• breast cancer involving factors crucial for their mechanism of action are reported across the literature [66][67]. This suggests that such acquired resistance might also become a common problem in advanced NSCLC treatment [68]. Some of the potential factors of resistance, such as poor internalization

• nanosized drug delivery carriers: Mixed-layer and multilayered nanocarriers with bioresponsive and cleavable layers, possessing different functional properties for improving the enhanced permeability and retention (EPR) effect, diffusion in the tumor microenvironment, cellular internalization and

Structural, optical, and bioimaging characterization of carbon quantum dots solvothermally synthesized from o-phenylenediamine

• Zoran M. Marković,
• Milica D. Budimir,
• Martin Danko,
• Dušan D. Milivojević,
• Pavel Kubat,
• Danica Z. Zmejkoski,
• Vladimir B. Pavlović,
• Marija M. Mojsin,
• Milena J. Stevanović and
• Biljana M. Todorović Marković

Beilstein J. Nanotechnol. 2023, 14, 165–174, doi:10.3762/bjnano.14.17

• test internalization of CQDs, Hela cells were treated for 48 h with a concentration of 200 µg/mL CQDs. As shown in Figure 6b, fluorescence imaging demonstrated that CQDs penetrated Hela cells well (compared to Hela cells treated with vehicle control, shown in Figure 6a) and were mainly in the cytoplasm

Facile preparation of Au- and BODIPY-grafted lipid nanoparticles for synergized photothermal therapy

• Yuran Wang,
• Xudong Li,
• Haijun Chen and
• Yu Gao

Beilstein J. Nanotechnol. 2022, 13, 1432–1444, doi:10.3762/bjnano.13.118

• ), indicating that BDP has good stability under these release conditions. Cellular uptake of AB-LNPs Efficient cellular internalization of drugs is critical to the anticancer therapeutic effects [26][27]. From the above studies, we found that DSPE-DTPA/Au3+/BDP at a molar ratio of 2:1:1 could form uniform

• the successful endocytosis of AB-LNPs into 4T1 cells. However, free BDP did not show time-dependent cellular uptake (Figure 4c,d). Compared with free BDP, AB-LNPs showed significantly enhanced uptake efficiency, indicating that the nanoparticles can increase the internalization and accumulation of

• drugs inside the cancer cells. The internalization of BDP or AB-LNPs in 4T1 cells was also observed by CLSM. The intracellular fluorescence signals of 4T1 cells treated with AB-LNPs were brighter than that of free BDP, indicating the enhanced internalization of BDP through entrapping in lipid

Gelatin nanoparticles with tunable mechanical properties: effect of crosslinking time and loading

• Agnes-Valencia Weiss,
• Daniel Schorr,
• Julia K. Metz,
• Metin Yildirim,
• Saeed Ahmad Khan and
• Marc Schneider

Beilstein J. Nanotechnol. 2022, 13, 778–787, doi:10.3762/bjnano.13.68

• internalization, the stiffer particles show significantly faster kinetics [6]. Similar results could be shown in an experimental approach by Hui et al. in a study with silica nanocapsules. Softer particles showed a greater deformation, resulting in a slower and less efficient uptake for softer particles [7

Theranostic potential of self-luminescent branched polyethyleneimine-coated superparamagnetic iron oxide nanoparticles

• Rouhollah Khodadust,
• Ozlem Unal and
• Havva Yagci Acar

Beilstein J. Nanotechnol. 2022, 13, 82–95, doi:10.3762/bjnano.13.6

• MCF7 and HCT116 than to HeLa cells at the tested dose of 19.2 µg/mL. Such cell line-based differences are normal since the mechanism of nanoparticle internalization may vary depending on the cell type, cell cycle stage, and cell polarization state [62]. Free Erb did not cause any significant

• modification may change the internalization pathway of the nanoparticles. As an example, in 2009, Gabrielson et al. demonstrated that folic acid modification of PEI polyplex enhances internalization via a caveolar pathway in cells expressing folate receptors [64]. Since caveolae-mediated internalization

• to demonstrate Erb specific internalization of nanoparticles by the target cells, both Erb and the cargo were used in nontoxic concentrations. Fluorescence microscopy images of nanoparticle treated cells indicate that the transfection with SPION@bPEI was not efficient at either dose or N/P ratios

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

• higher bioavailability and better internalization of anticancer drugs when loaded on ferrite NPs. Treated cells also exhibited morphological alterations such as cellular shrinkage and elongation which may affect their ability to metastasize (i.e., to adhere, migrate, and invade) [38]. PMA-coated NPs

• interaction between NPs a plasma membrane associated proteins [55]. In addition, the charge of polymeric coatings also governs NP uptake by cells. Positively charged polymers have been reported to enhance genotoxicity due to better internalization of NPs via the plasma membrane (electrostatic interaction) and

• death, respectively. The obtained results suggested better internalization of drug-loaded NPs compared to free drugs. Functionalized MFe2O4 NPs cause inhibition of MDR pump activity in treated HepG2 and HT144 cells Due to the overexpression of P-glycoprotein (P-gp), cancer cells possess the ability to

pH-driven enhancement of anti-tubercular drug loading on iron oxide nanoparticles for drug delivery in macrophages

• Karishma Berta Cotta,
• Sarika Mehra and
• Rajdip Bandyopadhyaya

Beilstein J. Nanotechnol. 2021, 12, 1127–1139, doi:10.3762/bjnano.12.84

• identical treatment conditions (Figure 6a). The increased uptake could be due to active engulfment of nanoparticles by macrophages, due to their larger size (20–120 nm size range) and surface charge (+29 mV or −16.5 mV) [46], which results in simultaneous internalization of larger amounts of drug. Figure 6b

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

• internalization, as compared to conventional therapies, potentially increasing therapeutic efficacy and minimizing side effects [4]. Nanosystems can be referred to as nanocarriers, nanoformulations, nanosized-delivery systems, and other similar terms. They have been utilized in the design of cellular and

• advantages of these systems have been evidenced by the significant increase in the in vivo performance of drugs administered in this way [47]. For instance, CUR nanocrystals obtained by solution-enhanced dispersion via supercritical CO2 showed increased internalization and apoptotic effects in colorectal

• associated with smaller sizes and possible internalization by endocytosis (particles with sizes <150 nm can be internalized by clathrin- or caveolin-mediated endocytosis), while particles with sizes from 250 nm to 3 µm can be internalized by macropinocytosis and phagocytosis. Lipid–polymer hybrid

The role of deep eutectic solvents and carrageenan in synthesizing biocompatible anisotropic metal nanoparticles

• Nabojit Das,
• Akash Kumar and
• Raja Gopal Rayavarapu

Beilstein J. Nanotechnol. 2021, 12, 924–938, doi:10.3762/bjnano.12.69

• the capping agent used) and the cell type used for toxicity assessment. Chan and co-workers reported that cell internalization is optimum for nanoparticles with a size of 40–50 nm [59]. This is due to maximum interaction between antibody and receptor during receptor-mediated endocytosis. In vitro

• determining toxicity and cell internalization of nanoparticles due to capping agents is critical. It has been reported that glutathione-capped gold nanoparticles underwent efficient cell internalization and efficient renal clearance compared to PEGylated and citrate-capped gold nanoparticles [68][69]. This

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

• vessels, and then recognize the specific endothelial target to which it needs to firmly adhere. Afterward, the adhered NDDS should induce endocytosis-mediated internalization into the BM vascular sinus endothelium, which probably will result in carrier transcytosis towards the stroma [20] (Figure 1

• not internalized after antibody binding, the authors speculate that the NP-enriched cell membrane promotes some kind of “passive” internalization of the functionalized NPs. Protein tyrosine kinase 7 (PTK7) is a highly expressed receptor in AML cells and is mostly assigned to granulocytic lineage

• of action, mAbs against EGFR competitively inhibit ligands, promote receptor internalization, and prolong downregulation induction. Antibody-dependent cell-mediated cytotoxicity and, to a lesser extent, complement-mediated cytotoxicity are the mechanisms of the therapeutic action of mAbs [71]. Used

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

• understood yet. Herein, we present a mechanistic study of cellular internalization pathways of two magnetic iron oxide nanoparticles (MNPs) differing in surface chemistry into A549 cells. The MNP uptake was investigated in the presence of different inhibitors of endocytosis and monitored by spectroscopic and

• involved in the internalization of polyethylene glycol-coated MNPs. Our data indicate that surface engineering can contribute to an enhanced delivery efficiency of nanoparticles. Keywords: bovine serum albumin; cellular uptake; magnetic iron oxide nanoparticles; polyethylene glycol; surface coating

• easily manufactured and biocompatible. Also, there are physiologically well tolerated as iron is an essential nutrient for almost all life forms [6]. Iron oxide nanoparticles are the only one FDA-approved magnetic nanoparticles for biomedical application (Resovist). Efficient cellular internalization of

The nanomorphology of cell surfaces of adhered osteoblasts

• Christian Voelkner,
• Mirco Wendt,
• Regina Lange,
• Max Ulbrich,
• Martina Gruening,
• Susanne Staehlke,
• Barbara Nebe,
• Ingo Barke and
• Sylvia Speller

Beilstein J. Nanotechnol. 2021, 12, 242–256, doi:10.3762/bjnano.12.20

• have been observed for dendritic cells. It has been shown that these structures serve as catchers for T cells [31]. Ruffles have been described on osteoblasts upon exposure to parathyroid extract [32] and after internalization of polymer or metal particles [33], on fibroblastoid cells [29][34], on

• breast cancer cells [30], and on keratinocytes [35]. In general, these features are associated with migration, receptor internalization, and micropinocytosis [30][36][37]. Membrane ruffling is regulated by a distinct signaling pathway [38] and the supporting actin is denser and more cross-linked [35

PEG/PEI-functionalized single-walled carbon nanotubes as delivery carriers for doxorubicin: synthesis, characterization, and in vitro evaluation

• Shuoye Yang,
• Zhenwei Wang,
• Yahong Ping,
• Yuying Miao,
• Yongmei Xiao,
• Lingbo Qu,
• Lu Zhang,
• Yuansen Hu and
• Jinshui Wang

Beilstein J. Nanotechnol. 2020, 11, 1728–1741, doi:10.3762/bjnano.11.155

• antitumor activity. Furthermore, fluorescence detection and flow cytometry (FCM) analysis results indicated that the internalization into cells of CNTs-PEG-PEI was significantly enhanced, thus inducing tumor cell death through apoptosis more efficiently. The above series of benefits of CNTs-PEG-PEI may be

• , SanJose), with 488 nm wavelength excitation and 590 nm wavelength emission, and untreated cells were used as blank. Fluorescence observation of the cellular internalization was also conducted. In brief, cells were seeded into 24-well plates, after complete attachment, fresh serum-free medium containing

• detect and observe the fluorescence signal in cells. Further, confocal laser scanning microscopy (CLSM) was utilized to observe the internalization. Cells were seeded into 6-well plates and incubated for 24 h. After co-incubation in 2 mL of medium containing free DOX or DOX-loaded nanocarrier

Cardiomyocyte uptake mechanism of a hydroxyapatite nanoparticle mediated gene delivery system

• Hiroaki Komuro,
• Masahiro Yamazoe,
• Kosuke Nozaki,
• Akiko Nagai and
• Tetsuo Sasano

Beilstein J. Nanotechnol. 2020, 11, 1685–1692, doi:10.3762/bjnano.11.150

• , this method may provide a solution to the current problem of using calcium phosphate. The cellular uptake performance is important for a successful vector-mediated gene transfection. In the cellular uptake process, the internalization pathway is an essential factor to prevent the fate of lysosomal

• -mediated endocytosis were not involved in the internalization of HAp by HL-1 cells. However, the cellular uptake efficiency of HAp was reduced by 50% and 79% upon cytochalasin D and EIPA treatment, respectively, when compared to non-treated cells. These results revealed the importance of macropinocytosis

• internalize HAp nanoparticles and the mechanism through which these cells performed the internalization. First, the results from transfection efficiency experiments indicated that HAp nanoparticles had a higher gene transfection efficiency in cardiomyocytes than they had in ECs. As shown in previous reports

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

• endocytic vesicles have been identified and described in the brain endothelial cells: clathrin-coated pits, caveolae and macropinocytosis vesicles. Clathrin-coated pits are involved in most of the internalization processes mediated by receptors such as TfR or insulin receptors [39][40]. After endocytosis

• [39]. The intracellular pathway taken by the vesicles depends on the receptor, on the internalization pathway (clathrin-mediated or caveolae) and also on the type of ligand binding to the receptors [39]. Furthermore, it has been shown that bEND3 cells (mouse brain microvascular cell line) had less

• , resulting in an overall net positive charge [108][126]. CPPs are able to enhance membrane penetration and cell internalization of their conjugated cargo in a large variety of cells, through pathways not always well known [126][127]. In the case of BBB crossing, their positive charge might induce their

Luminescent gold nanoclusters for bioimaging applications

• Nonappa

Beilstein J. Nanotechnol. 2020, 11, 533–546, doi:10.3762/bjnano.11.42

• . Review Luminescent gold nanoclusters Luminescent AuNCs show high photostability and biocompatibility and are nontoxic [41]. Their size is highly precise and small compared to QDs, offering a better internalization in cells and tissues [42][43][44][45][46][47]. The presence of surface ligands allows for a

• of streptavidin with biotin was exploited for imaging human hepatoma cells (HepG2, Figure 4C). HepG2 are cancerous cells that contain excess biotin. Retnakumari et al. studied the surface functionalization of Au-BSA NCs with folic acid (FA) for selective binding, internalization and imaging of folate

• , HeLa, HepG2 and A375, as well as a normal HEK cell line (Figure 5B). Confocal imaging confirmed the internalization of the nanocarriers. After incubating the cell lines with sodium azide, there was a decrease by 82% of uptake of the nanocarriers, suggesting that the internalization is through

Multilayer capsules made of weak polyelectrolytes: a review on the preparation, functionalization and applications in drug delivery

• Varsha Sharma and
• Anandhakumar Sundaramurthy

Beilstein J. Nanotechnol. 2020, 11, 508–532, doi:10.3762/bjnano.11.41

Brome mosaic virus-like particles as siRNA nanocarriers for biomedical purposes

• Alfredo Nuñez-Rivera,
• Pierrick G. J. Fournier,
• Danna L. Arellano,
• Ana G. Rodriguez-Hernandez,
• Rafael Vazquez-Duhalt and
• Ruben D. Cadena-Nava

Beilstein J. Nanotechnol. 2020, 11, 372–382, doi:10.3762/bjnano.11.28

• distribution [6], limitations in the blood flow of tumor vessels [7], pressure gradients, cellular internalization [8], and the escape of endosomal and lysosomal compartments and drug efflux pumps [9]. The use of nanoparticles as nanovehicles has been proposed to overcome some of these limitations

• properties of biomedical interest are demonstrated, such as biocompatibility, tumor cell internalization, and their efficiency as nanocarriers for siRNA delivery. In addition, the capacity of the BMV and CCMV viruses to modulate the immune response in vitro was also analyzed. Results and Discussion Cell

• internalization of VLPs In order to test the cell internalization of VLPs, BMV and CCMV VLPs were loaded with NanoOrange, a hydrophobic fluorescent dye. Both BMV and CCMV viruses have hydrophobic residues in their capsid protein in which hydrophobic molecules, such as NanoOrange, are bound. Due to the high

Poly(1-vinylimidazole) polyplexes as novel therapeutic gene carriers for lung cancer therapy

• Gayathri Kandasamy,
• Elena N. Danilovtseva,
• Vadim V. Annenkov and
• Uma Maheswari Krishnan

Beilstein J. Nanotechnol. 2020, 11, 354–369, doi:10.3762/bjnano.11.26

• internalization and escaped the endosome effectively. The polyplex was more effective than free siRNA in silencing VEGF in lung cancer cells. The silencing of VEGF was quantified using Western blot and was also reflected in the depletion of HIF-1α levels in the cells treated with the polyplex. VEGF silencing by

• incubated for 48 h. The cell viability was then assessed using the MTS reagent as described above. Internalization studies: Internalization of the polyplex in A549 cells was studied with Cy3 fluorophore-tagged siRNA. A549 cells at a seeding density of 105 cells/well were cultured on a cover slip in a 6-well

• good serum stability of the polyplex. In vitro studies The internalization of the polyplex in A549 cells was determined and the results are presented in Figure 3. It is observed that the PVI polyplexes accumulate on the membrane surface after 15 min and are starting to be internalized into the cells

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

• size, charge, and shape, affect the mechanisms cells use for their internalization. Technical difficulties in characterizing these mechanisms are presented. A better understanding of the first interactions of nano-sized materials with cells will help to design nanomedicines with improved targeting

• drugs currently present on the market [5]. This enables nanomedicines to potentially overcome problems associated with the passive diffusion of small molecular drugs through cell membranes, such as their indiscriminate internalization in different cell types and organs, which is often associated with

• system, blood circulation time, biodistribution, and cellular recognition and internalization can be tailored [1][2][3][7][8]. Moreover, the surface of nanomedicines can be engineered by introducing functional groups to reduce clearance and increase biodistribution, as well as for active targeting

Facile biogenic fabrication of hydroxyapatite nanorods using cuttlefish bone and their bactericidal and biocompatibility study

• Satheeshkumar Balu,
• Manisha Vidyavathy Sundaradoss,
• Swetha Andra and
• Jaison Jeevanandam

Beilstein J. Nanotechnol. 2020, 11, 285–295, doi:10.3762/bjnano.11.21

• porosity and high surface-to-volume ratio when compared to spherical nanometer-sized Hap particles, which facilitates interconnectivity and improves targeted cell internalization efficiency [22]. Thus, the aim of the present work is to use a simple, facile, unique, safe and cost-effective precipitation