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

• facilitates LNP binding to LDL receptors, which in turn leads to the uptake of the decorated particles by hepatocytes in the liver [25]. Therefore, we investigated the effects of heat inactivation on the stability of ApoE. We used recombinant ApoE3 for these studies, as it is the predominant form of ApoE in

A formulation containing Cymbopogon flexuosus essential oil: improvement of biochemical parameters and oxidative stress in diabetic rats

• Ailton Santos Sena-Júnior,
• Cleverton Nascimento Santana Andrade,
• Pedro Henrique Macedo Moura,
• Jocsã Hémany Cândido dos Santos,
• Cauãn Torres Trancoso,
• Eloia Emanuelly Dias Silva,
• Deise Maria Rego Rodrigues Silva,
• Ênio Pereira Telles,
• Luiz André Santos Silva,
• Isabella Lima Dantas Teles,
• Sara Fernanda Mota de Almeida,
• Daniel Alves de Souza,
• Jileno Ferreira Santos,
• Felipe José Aidar Martins,
• Ana Mara de Oliveira e Silva,
• Sandra Lauton-Santos,
• Guilherme Rodolfo Souza de Araujo,
• Cristiane Bani Correa,
• Rogéria De Souza Nunes,
• Lysandro Pinto Borges and
• Ana Amélia Moreira Lira

Beilstein J. Nanotechnol. 2025, 16, 617–636, doi:10.3762/bjnano.16.48

• disorganization was evident, with hepatocytes (H) arranged irregularly, many of them showing vacuolized cytoplasm, indicating cell degeneration, as well as pyknotic nuclei, reflecting large-scale cell death. The presence of a chronic inflammatory infiltrate was a striking finding, characterized by the

• indicate an attempt by the body to repair the damaged tissue, although in severe cases such as the one observed, liver regeneration may be insufficient to restore the organ’s homeostasis. Another relevant aspect was the presence of vacuolar degeneration of hepatocytes, characterized by the accumulation of

• pathological conditions. In addition, cell edema (B) was found, characterized by swelling of the hepatocytes due to excessive accumulation of intracellular fluid. This alteration may be associated with dysfunctions in the permeability of the plasma membrane, leading to an osmotic imbalance, which favors fluid

Liver-targeting iron oxide nanoparticles and their complexes with plant extracts for biocompatibility

• Shushanik A. Kazaryan,
• Seda A. Oganian,
• Gayane S. Vardanyan,
• Anatolie S. Sidorenko and
• Ashkhen A. Hovhannisyan

Beilstein J. Nanotechnol. 2024, 15, 1593–1602, doi:10.3762/bjnano.15.125

• (>100 nm). Smaller nanoparticles (<100 nm) are captured in the space of Disse, from where, if suitably functionalized, they can also accumulate in hepatocytes [34]. It has been shown that Fe3O4 NPs functionalized with salicylic acid (35 mg/kg body weight) can accumulate in the liver and exhibit

• . Histological analysis of morphological changes in liver tissue In the histological examination of the toxic effects of the agents in all groups, a characteristic architecture typical of the liver was observed, with preserved lobular structure and radial arrangement of hepatocytes, as well as normal blood

• vessel filling (Figure 5). However, in groups II and V, mildly pronounced dystrophic changes are observed in individual hepatocytes, that is, cytoplasmic opacity and the presence of optically distinguishable vacuoles; whereas in group IV, these dystrophic changes are observed in the majority of

Recent updates in applications of nanomedicine for the treatment of hepatic fibrosis

• Damai Ria Setyawati,
• Fransiska Christydira Sekaringtyas,
• Riyona Desvy Pratiwi,
• A’liyatur Rosyidah,
• Rohimmahtunnissa Azhar,
• Nunik Gustini,
• Gita Syahputra,
• Idah Rosidah,
• Etik Mardliyati,
• Tarwadi and
• Sjaikhurrizal El Muttaqien

Beilstein J. Nanotechnol. 2024, 15, 1105–1116, doi:10.3762/bjnano.15.89

• dynamic endothelial fenestrations to reach HSCs in the perisinusoidal space or even hepatocytes [24][29]. Smaller nanocarriers (10–20 nm) can be taken up rapidly by hepatocytes [32]. Besides the size of the administered nanocarriers, surface properties also play an important role in dictating

• hepatobiliary clearance in vivo. For example, positively charged mesoporous silica NPs (MSNPs) underwent significant uptake by hepatocytes, while MSNPs with negative charges were rapidly internalized by Kupffer cells in liver sinusoids [33]. The negative charge of the nanocarriers could facilitate efficient

• decoration with polyethylene glycol (PEG) may minimalize the uptake of nanocarriers by Kupffer cells, and such PEGylated nanocarriers are likely taken up by hepatocytes [36][37][38][39]. Besides augmenting hydrophilicity through PEGylation, stealth properties could be endowed to the nanocarriers through 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

• (Kupffer cells, i.e., the liver macrophages, liver sinusoidal endothelial cells (LSEC), and hepatocytes) in NP uptake [81]. A very recent study points to the importance of interactions between PEG-NPs with (apo)lipoproteins and scavenger receptors, and postulates that the high presence of these receptors

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

• CD163 is probably within the β chain of Hb (binding of Hb to Hp via a binding site within the Hb α chain) [27]. Furthermore, not only cells of the monocyte/macrophage lineage appear to be involved in sequestering Hb, but also hepatocytes [25][26]. It can be speculated that the same could be true for

• after a short while in the MRI scan [24]. While the authors hypothesized that the HBOC was taken up by CD163-expressing Kupffer cells/macrophages, Chow et al. reported that when isolated rat livers were perfused with a HBOC solution, hepatocytes also took up abundant hemin, as determined by heme

• oxygenase-1 expression [25]. Goldfischer et al. observed immunohistochemically the presence of Hb in phagocytic but also hepatocytic lysosomes [49]. Hepatocytes, however, do not express CD163; therefore; they must have a currently still unknown mechanism potentially for Hb recognition, but surely for HBOC

Fate and transformation of silver nanoparticles in different biological conditions

• Barbara Pem,
• Marija Ćurlin,
• Darija Domazet Jurašin,
• Valerije Vrček,
• Rinea Barbir,
• Vedran Micek,
• Raluca M. Fratila,
• Jesus M. de la Fuente and
• Ivana Vinković Vrček

Beilstein J. Nanotechnol. 2021, 12, 665–679, doi:10.3762/bjnano.12.53

• high concentration of chloride ions catalyse a controlled recrystallization of AgNPs. They observed structures similar to the forms presented in Figure 2b. As these large cubic and ball-like structures were not located inside hepatocytes, but extracellularly, we concluded that the crystallization of

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

• -vinylimidazole) chains modified with aminoethyl groups demonstrated excellent DNA binding ability in synergy with lactosylated poly(ʟ-lysine). This system was found to exhibit excellent gene transfection ability specifically in hepatocytes through interactions with the asialoglycoprotein receptor expressed on

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

• of 100 nm silica nanoparticles incubated with human serum were found to interact with their corresponding receptors, low-density lipoprotein receptor and Fc-gamma receptor I, respectively [17]. Similarly, lipid nanoparticles were efficiently targeted to the hepatocytes upon adsorption of apoE on

Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

• Yue Zhang and
• Wan-Xi Yang

Beilstein J. Nanotechnol. 2016, 7, 675–684, doi:10.3762/bjnano.7.60

• stress found that without shear stress, the cellular uptake/association of both PDA-coated liposomes (LPDA) and LPDA-PEG for hepatocytes were quite similar, while myoblasts preferred to internalize/associate with LPDA. However, under shear stress, hepatocytes showed its preference to LPDA after 30 min

Overview about the localization of nanoparticles in tissue and cellular context by different imaging techniques

• Anja Ostrowski,
• Daniel Nordmeyer,
• Alexander Boreham,
• Cornelia Holzhausen,
• Lars Mundhenk,
• Christina Graf,
• Martina C. Meinke,
• Annika Vogt,
• Sabrina Hadam,
• Jürgen Lademann,
• Eckart Rühl,
• Ulrike Alexiev and
• Achim D. Gruber

Beilstein J. Nanotechnol. 2015, 6, 263–280, doi:10.3762/bjnano.6.25

• to their negatively charged, sulfate rich shell. Organic dPGS amine accumulated in the cytoplasm of hepatic Kupffer cells (c, arrow). These liver specific macrophages are identified by their comma-shaped nuclei and their lining of hepatic sinusoids. Adjacent hepatocytes (c, asterisks) appear as light

• were clearly associated with the red pulp but not within lymphoid follicles (spared dots). (c) Light microscopic autoradiography with numerous radioactive decay-induced signals over Kupffer cells (arrows) in the liver of a mouse (left panel). Signals were sparse in adjacent hepatocytes with larger

The distribution and degradation of radiolabeled superparamagnetic iron oxide nanoparticles and quantum dots in mice

• Denise Bargheer,
• Artur Giemsa,
• Barbara Freund,
• Markus Heine,
• Christian Waurisch,
• Gordon M. Stachowski,
• Stephen G. Hickey,
• Alexander Eychmüller,
• Jörg Heeren and
• Peter Nielsen

Beilstein J. Nanotechnol. 2015, 6, 111–123, doi:10.3762/bjnano.6.11

• the Zn pool was observed. Confocal microscopy of rat liver cryosections (prepared 2 h after intravenous injection of polymer-coated Qdots) revealed a colocalization with markers for Kupffer cells and liver sinusoidal endothelial cells (LSEC), but not with hepatocytes. In J774 macrophages, fluorescent

• colocalize with LSECs as well as with KCs. To date, polymer-coated Qdots were not found in hepatocytes. Since the surface chemistry of the Qdots and SPIOs is identical when coated with the amphiphilic polymer, the cell distribution should be similar. Intracellular processing of Qdots Further insight into the

• (LSECs, with anti-CD68) was performed. Regions outlined by the white boxes are magnified in the lower panels. Nanoparticles can be found located in endothelial cells (A) as well as in Kupffer cells (B), but not in hepatocytes. Scale bar: 20 µm for the upper panel, and 5 µm for the magnified images

The fate of a designed protein corona on nanoparticles in vitro and in vivo

• Denise Bargheer,
• Julius Nielsen,
• Gabriella Gébel,
• Markus Heine,
• Sunhild C. Salmen,
• Roland Stauber,
• Horst Weller,
• Joerg Heeren and
• Peter Nielsen

Beilstein J. Nanotechnol. 2015, 6, 36–46, doi:10.3762/bjnano.6.5

• a role also in a specific uptake for example in hepatocytes. Discussion Many experimental techniques have been used to investigate the binding of proteins to nanoparticles and some models have been proposed to rationalize the experiments [10][32]. The most accepted view on protein corona formation

The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver

• Markus Heine,
• Alexander Bartelt,
• Oliver T. Bruns,
• Denise Bargheer,
• Artur Giemsa,
• Barbara Freund,
• Ludger Scheja,
• Christian Waurisch,
• Alexander Eychmüller,
• Rudolph Reimer,
• Horst Weller,
• Peter Nielsen and
• Joerg Heeren

Beilstein J. Nanotechnol. 2014, 5, 1432–1440, doi:10.3762/bjnano.5.155

• process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα) or chemokine (C-X-C motif) ligand 10 (Cxcl10) indicated that 48 h after injection internalized nanocrystals did not provoke

• pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications. Keywords

• : hepatocytes; inflammation; Kupffer cells; liver sinusoidal endothelial cells; nanoparticle toxicity; nanoparticle uptake; quantum dots; superparamagnetic iron-oxide nanocrystals; Introduction The superior optical properties of QDs compared to organic dyes render them promising candidates for the demands of