Mechanistic insights into endosomal escape by sodium oleate-modified liposomes

• Ebrahim Sadaqa,
• Satrialdi,
• Fransiska Kurniawan and
• Diky Mudhakir

Beilstein J. Nanotechnol. 2024, 15, 1667–1685, doi:10.3762/bjnano.15.131

• inhibitor of caveolae-mediated endocytosis, also significantly reduced uptake (p < 0.001), suggesting the involvement of caveolae in the internalization of Unmodified-Lipo. Amiloride, which blocks macropinocytosis, had no significant effect (p < 0.99), indicating a negligible role for macropinocytosis in

• Unmodified-Lipo uptake. For SO-Lipo (Figure 2b,e), sucrose had no significant effect (p = 0.745), suggesting that SO shifts the uptake away from clathrin-mediated endocytosis. Amiloride significantly reduced uptake (p < 0.001), indicating that macropinocytosis is a key pathway for SO-Lipo, consistent with

• findings that fatty acids often use macropinocytosis for internalization [17]. Filipin significantly inhibited uptake (p < 0.001), showing that caveolae-mediated endocytosis also plays an important role in SO-Lipo uptake. These results align with reports that anionic particles undergo caveolae-mediated

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

• involved in macropinocytosis, the CLIC/GEEC (clathrin-independent carrier/glycosylphosphatidylinositol (GPI)-anchored protein-enriched endosomal compartments) pathway, as well as in FEME (fast endophilin-mediated endocytosis) and phagocytosis (an uptake mechanism for large particles mostly found in

• and flattens caveolae. However, cholesterol is required for a number of uptake mechanisms (Table 1), for instance for CME and macropinocytosis [35][36]. Most likely cholesterol will turn out to be required for all endocytic pathways. One function of cholesterol in the membrane is to decrease membrane

• shown to be internalized by different endocytic mechanisms [58][59][60]. Uptake via caveolae may be a minor route; introduction of caveolae in Caco-2 cells by transfection with caveolin did not increase the uptake of cholera toxin [58]. Macropinocytosis and nanoparticle uptake Several of the NPs studied

Curcumin-loaded albumin submicron particles with potential as a cancer therapy: an in vitro study

• Nittiya Suwannasom,
• Netsai Sriaksorn,
• Chutamas Thepmalee,
• Krissana Khoothiam,
• Ausanai Prapan,
• Hans Bäumler and
• Chonthida Thephinlap

Beilstein J. Nanotechnol. 2023, 14, 1127–1140, doi:10.3762/bjnano.14.93

• cancer cells, likely attributed to particle uptake through endocytosis pathways, including phagocytosis and macropinocytosis [51]. The uptake process depends on cell membrane and particle properties, including size, shape, composition, and surface properties. These factors play a crucial role in particle

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

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

• 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

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

• . Macropinocytosis, a clathrin- and caveolin-independent endocytosis pathway, occurs via actin-driven membrane protrusions. The large endocytic vesicle has a size bigger than 1 µm [13]. Alternative pathways of endocytosis involve other types of cholesterol-rich microdomains called “lipid rafts”, small structures of

• the uptake of nanomaterials [54]. In agreement with our results, Yumoto et al. [55] also determined the predominant uptake of fluorescently labeled albumin via CME in A549 cells. The authors supposed that macropinocytosis but not CavME may also be involved in albumin internalization. Similarly, the

• different endocytic pathways, for example, macropinocytosis as suggested by Rothen-Rutishauser et al. [50] or non-selective alternative endocytic structures, discussed by Boucrot et al. [64] or Vega et al. [65], could be upregulated to provide compensatory endocytic pathways. Unfortunately, the regulation

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

• are attributed to macropinocytosis events [47]. They may result from the collapse of circular dorsal ruffles. (c) Pancake-like structures, which were rarely observed, show plateau-like characteristics. The heights observed are similar to those of dorsal ruffles. (d–f) The corresponding line profiles

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

• vector for transfecting cardiomyocyte-derived HL-1 cells. HAp exhibited particles on the nanoscale and with a low cytotoxicity in HL-1 cells. The transfection assay performed with several endocytosis inhibitors suggested that the HAp/pDNA complexes were internalized by HL-1 cells through macropinocytosis

• . Furthermore, this HL-1 cell uptake was generated in response to HAp stimulation. Thus, HAp is a positive regulator of macropinocytosis in HL-1 cells and a good system for gene delivery in cardiomyocytes. Keywords: cardiomyocyte; endocytosis; gene delivery system; hydroxyapatite nanoparticles

• ; macropinocytosis; Introduction Heart disease is one of the major causes of death and accounts for approximately one in every three deaths worldwide every year [1]. Since cardiomyocytes have very limited regenerative functions, the heart becomes fibrotic after the cardiomyocytes become damaged during certain

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

• clathrin and/or caveolae pits, RhoA, CDC42, ARF6, or flotillin-mediated endocytosis/phagocytosis and receptor-independent macro- and micropinocytosis (for reviews on the endocytosis of nanoparticles see [105][106]). Macropinocytosis is not selective and can take up spheres with a diameter of up to 1 mm [81

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

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

• surface is not a limiting factor for the cell internalization of BMV and CCMV. Thus, it seems possible that the capsid internalization could be carried out by macropinocytosis, a process independent of vimentin. Biocompatibility of CCMV and BMV A possible virus cytotoxicity was evaluated. BMV and CCMV

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

• especially in the uptake of larger objects [90] via this pathway. Next to CME, several clathrin-independent endocytic (CIE) pathways have been described [71][91][92]. One of these pathways is macropinocytosis, which cells use to internalize larger volumes of extracellular fluids and solutes. In

• macropinocytosis, extracellular fluids are engulfed by membrane ruffles and protrusions. Formation of these ruffles requires actin nucleation and in some cells also cholesterol [93][94]. Another frequently studied clathrin-independent pathway is the so-called caveolae-mediated endocytosis. Caveolae are 50–80 nm

• predominantly internalized through clathrin-mediated endocytosis, with a fraction of particles utilizing macropinocytosis, while negatively charged nanoparticles are more likely to use a cholesterol-dependent mechanism for their internalization [21][141]. Contradicting results were reported in which clathrin

Internalization mechanisms of cell-penetrating peptides

• Ivana Ruseska and
• Andreas Zimmer

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

• and is restricted to specialized cells (macrophages, monocytes and neutrophils). Pinocytosis, on the other hand, involves the uptake of fluids and solutes and occurs in all cells. At least four different mechanisms have been described for pinocytosis: macropinocytosis, clathrin-mediated endocytosis

• the active transport of CPPs emerged. Most of the older studies conducted on this matter as well as more recent ones suggest macropinocytosis as the main entry path for CPPs into cells [55][56][57][58][59]. Table 2 summarizes the endocytic mechanisms used by each CPP conjugate mentioned in the

• following text. Macropinocytosis as an entry mechanism Macropinocytosis is a rapid, lipid raft-dependent and receptor-independent form of endocytosis [60]. It is a process accompanying the membrane ruffling induced in many cell types upon stimulation by growth factors or other signals. Macropinocytosis

Characterization and influence of hydroxyapatite nanopowders on living cells

• Przemyslaw Oberbek,
• Tomasz Bolek,
• Adrian Chlanda,
• Seishiro Hirano,
• Sylwia Kusnieruk,
• Julia Rogowska-Tylman,
• Ganna Nechyporenko,
• Viktor Zinchenko,
• Wojciech Swieszkowski and
• Tomasz Puzyn

Beilstein J. Nanotechnol. 2018, 9, 3079–3094, doi:10.3762/bjnano.9.286

• phenomenon was observed for other materials (images not shown). Observations confirmed that hydroxyapatite agglomerates can be easily taken up by the cells [20][23][61] (probably through macropinocytosis or phagocytosis). Figure 7c presents characteristic spherical agglomerates of hydroxyapatite F202

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

• , which can be subdivided into macro- and microscale processes [8]. The first, phagocytosis, involves the ingestion of large particles: NPs or agglomerates typically larger than 0.25 μm in diameter. The second, pinocytosis, includes micro- and macropinocytosis, clathrin-, and caveolin-mediated endocytosis

Nano-engineered skin mesenchymal stem cells: potential vehicles for tumour-targeted quantum-dot delivery

• Liga Saulite,
• Dominyka Dapkute,
• Karlis Pleiko,
• Ineta Popena,
• Simona Steponkiene,
• Ricardas Rotomskis and
• Una Riekstina

Beilstein J. Nanotechnol. 2017, 8, 1218–1230, doi:10.3762/bjnano.8.123

• (CPZ), phagocytosis inhibitor cytohalasin D (CytD), macropinocytosis inhibitor ethylisopropyl amiloride (EIPA) (Cayman Chemical, USA), caveolin/lipid raft-mediated endocytosis inhibitor nystatin and caveolin-dependent endocytosis inhibitor dynasore (all from Sigma-Aldrich, USA, unless otherwise stated

Uptake of the proteins HTRA1 and HTRA2 by cells mediated by calcium phosphate nanoparticles

• Olga Rotan,
• Katharina N. Severin,
• Simon Pöpsel,
• Alexander Peetsch,
• Melisa Merdanovic,
• Michael Ehrmann and
• Matthias Epple

Beilstein J. Nanotechnol. 2017, 8, 381–393, doi:10.3762/bjnano.8.40

• that the main internalization pathway for anionic calcium phosphate nanoparticles into HeLa cells was macropinocytosis. In that case, cationic nanoparticles were also taken up much better than anionic nanoparticles [47]. This is also supported by earlier studies on the uptake of nanoparticles with

Improved biocompatibility and efficient labeling of neural stem cells with poly(L-lysine)-coated maghemite nanoparticles

• Igor M. Pongrac,
• Marina Dobrivojević,
• Lada Brkić Ahmed,
• Michal Babič,
• Miroslav Šlouf,
• Daniel Horák and
• Srećko Gajović

Beilstein J. Nanotechnol. 2016, 7, 926–936, doi:10.3762/bjnano.7.84

• of neural stem cells. Cytochalasine D blocked the cellular uptake of nanoparticles indicating an actin-dependent process, such as macropinocytosis, to be the internalization mechanism for both nanoparticle types. Finally, immunocytochemistry analysis of neural stem cells after treatment with poly(L

• ®-D-spio nanoparticles, NSCs were treated with different endocytotic inhibitors, incubated with nanoparticles and subsequently, flow cytometry analysis of the labeled cells was performed (Figure 7A,B). The inhibitors were cytochalasine D (blocks actin-dependent process such as macropinocytosis

• process, e.g., macropinocytosis, was the mechanism of nanoparticle uptake for both types of nanoparticles. NSC progenitor post-labeling phenotype and neural differentation potential NSCs treated with PLL-γ-Fe2O3 and nanomag®-D-spio nanoparticles for 48 h stained positive for nestin, a marker of neural

Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

• Lisa Landgraf,
• Ines Müller,
• Peter Ernst,
• Miriam Schäfer,
• Christina Rosman,
• Isabel Schick,
• Oskar Köhler,
• Hartmut Oehring,
• Vladimir V. Breus,
• Thomas Basché,
• Carsten Sönnichsen,
• Wolfgang Tremel and
• Ingrid Hilger

Beilstein J. Nanotechnol. 2015, 6, 300–312, doi:10.3762/bjnano.6.28

• by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of

• different nanoparticle formulations, we used different inhibitors to block the best-known internalization routes: clathrin-mediated, caveolae-mediated and macropinocytosis [46]. Microscopy data and the semi-quantitative analysis of the nanoparticle uptake behavior revealed a caveolae-dependent

• similar uptake behavior compared to the OCH3-functionalized gold colloids, indicating a clathrin- and macropinocytosis-dependent mechanism (Figure 7b). Our analysis of uptake mechanisms of different gold nanoparticle formulations confirms literature data, in which a clathrin- and macropinocytosis

The effect of surface charge on nonspecific uptake and cytotoxicity of CdSe/ZnS core/shell quantum dots

• Vladimir V. Breus,
• Anna Pietuch,
• Marco Tarantola,
• Thomas Basché and
• Andreas Janshoff

Beilstein J. Nanotechnol. 2015, 6, 281–292, doi:10.3762/bjnano.6.26

• II cells after 6 h of exposure. We used chlorpromazine to inhibit the formation of clathrin-coated pits through the assembly of clathrin and AP2 adaptor complexes in the endosomal membranes, 5-(N,N-dimethyl)amiloride hydrochloride (DMA). This prohibited macropinocytosis by blocking amiloride

• . Even though the DMA-treated cells still display interaction with DHLA–QDs and DPA–QDs, we cannot exclude that macropinocytosis was responsible for particle uptake, since all known pharmacological inhibitors have only limited efficiency for this receptor-independent endocytic pathway [35]. The behavior

• macropinocytosis), FPN: filipin III (inhibitor of caveolin-mediated endocytosis). Wide-field microscopy images and corresponding diffusion constants of 10 nM solutions of CA–QDs (a,d); DHLA–QDs (b,e); and DPA–QDs (c,f) added to MDCKII cells for 3.5–4 h (a–c) and 22–23 h (d–f). Each image is an overlay of 200

Mechanical properties of MDCK II cells exposed to gold nanorods

• Anna Pietuch,
• Bastian Rouven Brückner,
• David Schneider,
• Marco Tarantola,
• Christina Rosman,
• Carsten Sönnichsen and
• Andreas Janshoff

Beilstein J. Nanotechnol. 2015, 6, 223–231, doi:10.3762/bjnano.6.21

• attribute to a loss of plasma membrane due to enforced endocytostis. Frequently we found macropinocytosis and aggregation of CTAB-particles inside the cells. Membrane permeabilization was not observed. We propose that the positively charged particles initially adsorb on the negatively charged plasma

Caveolin-1 and CDC42 mediated endocytosis of silica-coated iron oxide nanoparticles in HeLa cells

• Nils Bohmer and
• Andreas Jordan

Beilstein J. Nanotechnol. 2015, 6, 167–176, doi:10.3762/bjnano.6.16

• [37] and mesoporous silica particles [40] exclusively through Clathrin mediated endocytosis and/or macropinocytosis. This discrepancy can be explained by the different physicochemical properties of the particles used. Especially in the field of iron-oxide nanoparticles more studies concerning the

• involved in many other cellular processes including macropinocytosis [45], therefore explaining its relevance in the uptake of polydisperse SPIONs. Depletion of PIP5Kα caused no significant effect. Conclusion This study shows for the first time, that Caveolin-1 and CDC42 play an important role in the

Mammalian cell growth on gold nanoparticle-decorated substrates is influenced by the nanoparticle coating

• Christina Rosman,
• Sebastien Pierrat,
• Marco Tarantola,
• David Schneider,
• Eva Sunnick,
• Andreas Janshoff and
• Carsten Sönnichsen

Beilstein J. Nanotechnol. 2014, 5, 2479–2488, doi:10.3762/bjnano.5.257

• with the negatively charged membrane [21][22], and to the sedimentation behavior of the particles which is related to their colloidal stability under physiological conditions [33]. The uptake was likely caused by non-specific endocytosis or macropinocytosis. Therefore, we expected an even stronger

Nanoparticle interactions with live cells: Quantitative fluorescence microscopy of nanoparticle size effects

• Li Shang,
• Karin Nienhaus,
• Xiue Jiang,
• Linxiao Yang,
• Katharina Landfester,
• Volker Mailänder,
• Thomas Simmet and
• G. Ulrich Nienhaus

Beilstein J. Nanotechnol. 2014, 5, 2388–2397, doi:10.3762/bjnano.5.248

• on the specific uptake machinery involved, these are macropinocytosis, clathrin- and caveolae-mediated endocytosis, and mechanisms that involve neither clathrin nor caveolae. The exposed functional groups on an NP surface interact with cell surface receptors and may activate the cell’s uptake

Effect of silver nanoparticles on human mesenchymal stem cell differentiation

• Christina Sengstock,
• Jörg Diendorf,
• Matthias Epple,
• Thomas A. Schildhauer and
• Manfred Köller

Beilstein J. Nanotechnol. 2014, 5, 2058–2069, doi:10.3762/bjnano.5.214

• through clathrin-dependent endocytosis and by macropinocytosis and that silver agglomerates were formed in the cytoplasm following the uptake of these nanoparticles [11]. There is a general consensus that dissolved silver ions are responsible for the majority of the biological effects on various cells and