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 MBs, leading to the term “microstream”. Depending on the US intensity, the oscillating MBs come into close proximity with the cells and induce stresses on the cell membrane [75]. Consequently, the triggered shear forces cause disruption of the cell membrane and increase intracellular uptake of

• proximity to the cell membrane. It has been shown that during inertial cavitation, in addition to direct oscillating MB–cell membrane interactions, a fluid microjet formed around the MBs can be responsible for providing secondary mechanical stress on the cell membrane and create transient disruption. In

• fact, microjets can act as a microsyringe for delivering drugs into the cytosol during the collapse phase of the MB cavitation [74]. The maximal distance between the MB and the cell membrane should not exceed one MB diameter in order to exert a significant impact on the cell membrane [78]. Yu et al

Recent progress in actuation technologies of micro/nanorobots

• Ke Xu and
• Bing Liu

Beilstein J. Nanotechnol. 2021, 12, 756–765, doi:10.3762/bjnano.12.59

• bilayers, which also contains an actuator and a clutch inside. When the robot is irradiated by ultraviolet light, the photoresponsive DNA will split into single strands and attach to the microtubules. The slide of microtubules causes the outer cell membrane to change shape, which transforms the robot from

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

• 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

• NALM-6 cell membrane vesicles that were further decorated with aTGFβRII antibodies, attached via hypoxia-sensitive azobenzene linker. The membrane coating plays a dual role in the formulation. It guides the drug to the BM via receptor–ligand interaction between CXCR4 (a chemokine receptor expressed on

Characterization, bio-uptake and toxicity of polymer-coated silver nanoparticles and their interaction with human peripheral blood mononuclear cells

• Sahar Pourhoseini,
• Reilly T. Enos,
• Angela E. Murphy,
• Bo Cai and
• Jamie R. Lead

Beilstein J. Nanotechnol. 2021, 12, 282–294, doi:10.3762/bjnano.12.23

• . However, for the AgNO3 treatment, this ratio increased in a dose-dependent manner (Table 2). Impact of PVP-AgNPs and Ag ions on viability and metabolic activity of PBMCs Cell membrane integrity as a marker for cell viability was measured by LDH release; a greater LDH release is an indication of more

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

• ) or the red signal (corresponding to free RITC-BSA-SO-MNPs) were mainly localized at the cell membrane while clathrin (green signal) was detected in the cytoplasm (Figure 3B and Figure 3C). These results confirmed the dominant role of CME in the internalization of BSA-coated MNPs. In the presence of

• Dyn, the signal of RITC-BSA-SO-MNPs and FITC–clathrin was co-localized on the cell membrane (yellow signal), indicating the accumulation of a fraction of nanoparticles in the clathrin-coated pits (Figure 3D). The pattern of the co-localization signal of RITC-BSA-SO-MNPs and FITC–clathrin implied that

• surface charge), cell membrane properties (fluidity, type of receptors, and receptor density), and cell type [30][31][32]. For biomedical applications, the optimal size of nanocarriers is in the range of 95–200 nm because of the higher accumulation rate in tumors [33][34]. Spherical nanoparticles (NPs) in

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

• aqueous medium intact, one may be tempted to conclude that ATP-driven or metabolic processes are responsible for the non-equilibrium character, that is, the larger extent of live cell membrane fluctuations [53][54][55]. Especially active membrane motions generated via the spectrin corset underneath the

• . (a, e) SICM topography images. The acquisition time was 68 min per image. Cell membrane protrusions, so-called ruffles, can be seen as bright spots. (b, f) Corresponding bright-field microscopy images of the living cell taken prior to the SICM measurements. The cell has been digitally stained in

• the cell nucleus. These tail-like features are characterized by heights of less than 100 nm and seem to show no flapping, which results in almost orthogonal orientation with respect to the cell membrane. (b) Depressions or holes in the cell membrane of ca. 500 nm depth. Similar features in literature

Imaging of SARS-CoV-2 infected Vero E6 cells by helium ion microscopy

• Natalie Frese,
• Patrick Schmerer,
• Martin Wortmann,
• Matthias Schürmann,
• Matthias König,
• Michael Westphal,
• Friedemann Weber,
• Holger Sudhoff and
• Armin Gölzhäuser

Beilstein J. Nanotechnol. 2021, 12, 172–179, doi:10.3762/bjnano.12.13

• . The HIM pictures show the three-dimensional appearance of SARS-CoV-2 and the surface of Vero E6 cells at a multiplicity of infection of approximately 1 with great morphological detail. The absence of a conductive coating allows for a distinction between virus particles bound to the cell membrane and

• bioimaging, especially for the imaging of interactions between viruses and their host organisms. Keywords: bioimaging; cell membrane; charge compensation; helium ion microscopy; SARS-CoV-2; Vero E6 cells; Introduction The last decade of helium ion microscopy (HIM) was characterized by a rapid exploration

• without any conductive coating. The presented images allow for the identification of SARS-CoV-2 virus particles, their interaction with the cell membrane and a distinction between virus particles bound to the cell surface from those lying on it. Experimental Vero E6 cells were cultivated in Dulbecco's

Effect of different silica coatings on the toxicity of upconversion nanoparticles on RAW 264.7 macrophage cells

• Cynthia Kembuan,
• Helena Oliveira and
• Christina Graf

Beilstein J. Nanotechnol. 2021, 12, 35–48, doi:10.3762/bjnano.12.3

• -aminopropyltrimethoxysilane (AHAPS), which provides the nanoparticle surface with a positive charge, increasing their interaction with the cell membrane. The particles were characterized by scanning transmission electron microscopy (STEM), dynamic light scattering (DLS), electrophoretic light scattering (ELS), and

• surface charge [51]. Positively charged silica particles interact more efficiently with the negatively charged cell membrane than negatively charged particles [45], which can also cause an enhanced uptake [51][52]. This process is supported by the fact that the hydrodynamic diameter of the AHAPS

• cells. In contrast, the amine-functionalized particles were only adsorbed onto the cell membrane. Similar results were also obtained by Kurtz-Chalot et al., in which SiO2 nanoparticles with a high positive charge were more adsorbed than taken up by cells compared to the corresponding non-modified

Bio-imaging with the helium-ion microscope: A review

• Matthias Schmidt,
• James M. Byrne and
• Ilari J. Maasilta

Beilstein J. Nanotechnol. 2021, 12, 1–23, doi:10.3762/bjnano.12.1

• mitotic HeLa cells that HIM is ready for ultrastructure research in cell biology. Research on the ultrastructure of cells with the HIM was subsequently continued by Schürmann et al., who presented HIM micrographs of cell-membrane nanodomains in mammalian cells [16]. HIM entered the field of virology in

• fixation in 4% formaldehyde, rinsing in buffer, dehydration with ethanol, and air-drying – did not suffice to maintain the ultrastructure of the cell membrane as well as the fine layer of EPS, which HIM can, in principle, visualise. In the context of the microscopic analysis of bacterial and archaeal

Antimicrobial metal-based nanoparticles: a review on their synthesis, types and antimicrobial action

• Matías Guerrero Correa,
• Fernanda B. Martínez,
• Cristian Patiño Vidal,
• Camilo Streitt,
• Juan Escrig and
• Carol Lopez de Dicastillo

Beilstein J. Nanotechnol. 2020, 11, 1450–1469, doi:10.3762/bjnano.11.129

• their excellent properties, CuO NPs have attracted great interest from the healthcare, food packaging, medical, and environmental industries [120][134]. This metal oxide is capable of disrupting the normal function of the cell membrane, changing its permeability and the cellular respiration process [135

• production and clearance of ROS in cells are balanced by those enzymatic systems. Nevertheless, when these reactive species are in excess, a set of redox reactions can lead to cell death by the alteration of different essential structures (such as cell membrane, DNA, proteins, and electron transport chain

• ) and metabolic routes which are responsible for maintaining the normal morphological and physiological cellular functions [153]. In addition to the oxidative stress, released metal ions from the metal oxide NPs can spread through the cell membrane into the cytoplasm and organelles. Metallic ions can

Thermophoretic tweezers for single nanoparticle manipulation

• Jošt Stergar and
• Natan Osterman

Beilstein J. Nanotechnol. 2020, 11, 1126–1133, doi:10.3762/bjnano.11.97

• thermophoresis and fluid flow can be used to highly concentrate (trap) nanoparticles and molecules [24][25]. Suspended biological cells can be easily thermophoretically manipulated by harnessing the permittivity gradient in the electric double layer of the charged surface of the cell membrane [26]. Optical

Examination of the relationship between viscoelastic properties and the invasion of ovarian cancer cells by atomic force microscopy

• Mengdan Chen,
• Jinshu Zeng,
• Weiwei Ruan,
• Zhenghong Zhang,
• Yuhua Wang,
• Shusen Xie,
• Zhengchao Wang and
• Hongqin Yang

Beilstein J. Nanotechnol. 2020, 11, 568–582, doi:10.3762/bjnano.11.45

• an important factor determining the mechanical properties of cells [50]. Some researchers have shown that alterations in the cytoskeletal structure or functional defects of cells are associated with the ability of tumor cells to proliferate [51]. The actin filaments on the cell membrane can affect

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

• , engineered nano-sized materials can exploit the cellular machinery to be internalized by cells. In fact, since the cell membrane blocks diffusion of complexes larger than ca. 1 kDa, nano-sized materials, such as nanomedicines, are transported into cells using energy-dependent mechanisms, unlike many small

• adsorbing on the nanoparticles once they are introduced in biological environments and the resulting corona can screen the targeting moieties [15][16]. At the same time, it has emerged that the corona itself can be recognized by receptors at the cell membrane [17][18] and that this initial recognition can

• the initial recognition at the cell membrane and the following mechanisms of internalization by cells. We discuss these aspects in relation to the application of nano-sized materials for nanomedicine. Challenges in characterizing these first events will be illustrated, together with a brief

Rational design of block copolymer self-assemblies in photodynamic therapy

• Maxime Demazeau,
• Laure Gibot,
• Anne-Françoise Mingotaud,
• Patricia Vicendo,
• Clément Roux and
• Barbara Lonetti

Beilstein J. Nanotechnol. 2020, 11, 180–212, doi:10.3762/bjnano.11.15

• second part. A third part will focus on the interactions between the vectors with the cell membrane, either in its native form or in biomimetic models. Finally, cellular entrance processes and intracellular targeting will also be described, showing possible intracellular targeting methods as well as the

Internalization mechanisms of cell-penetrating peptides

• Ivana Ruseska and
• Andreas Zimmer

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

• influence the cellular uptake mechanism. Keywords: cell-penetrating peptides; direct translocation; drug delivery; endocytosis; internalization; Introduction The cell membrane is a semipermeable barrier, serving as a protective layer for the cells. It is an essential organelle for cell survival and

• . Review Direct translocation through the cell membrane The direct translocation of CPPs through the cell membrane as an energy-independent mechanism and an alternative to endocytosis was suggested after internalization of CPPs was observed at low temperature [23]. As a process which requires no energy

• in a broad spectrum of cell lines. It has a length of 21 amino acids and consists of three domains, each conferring a specific function: (i) a hydrophobic, tryptophan-rich sequence required for the interaction with macromolecules and cell-membrane targeting, (ii) a hydrophilic sequence, rich in

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

• -Target-lipo group. Cells exposed to FL-Control-lipo displayed a diffuse cell membrane-like staining with few green fluorescent puncta. Whereas, the target-lipo exposed cells displayed many more fluorescent puncta as well as a widespread increase in cellular fluorescence. Our observations here indicate

Nitrogen-vacancy centers in diamond for nanoscale magnetic resonance imaging applications

• Alberto Boretti,
• Lorenzo Rosa,
• Jonathan Blackledge and
• Stefania Castelletto

Beilstein J. Nanotechnol. 2019, 10, 2128–2151, doi:10.3762/bjnano.10.207

Review of advanced sensor devices employing nanoarchitectonics concepts

• Katsuhiko Ariga,
• Tatsuyuki Makita,
• Masato Ito,
• Taizo Mori,
• Shun Watanabe and
• Jun Takeya

Beilstein J. Nanotechnol. 2019, 10, 2014–2030, doi:10.3762/bjnano.10.198

• recognition sites provided positive effects. It is a plausible mechanism regarding how biological molecular recognition occurs in aqueous media [155]. The molecular recognition of small molecules can be accomplished at certain kind of interfacial environments such as cell membrane, inside surfaces of

Synthesis and potent cytotoxic activity of a novel diosgenin derivative and its phytosomes against lung cancer cells

• Liang Xu,
• Dekang Xu,
• Ziying Li,
• Yu Gao and
• Haijun Chen

Beilstein J. Nanotechnol. 2019, 10, 1933–1942, doi:10.3762/bjnano.10.189

• , the phytosomes containing abundant phospholipids could carry amphiphilic agents to cross the cell membrane resulting in high intracellular drug concentrations, which might change the action mechanisms of P2. Conclusion Di derivatives were designed and P2 was screened. P2 showed better cytotoxic

Toxicity and safety study of silver and gold nanoparticles functionalized with cysteine and glutathione

• Barbara Pem,
• Igor M. Pongrac,
• Lea Ulm,
• Ivan Pavičić,
• Valerije Vrček,
• Darija Domazet Jurašin,
• Marija Ljubojević,
• Adela Krivohlavek and
• Ivana Vinković Vrček

Beilstein J. Nanotechnol. 2019, 10, 1802–1817, doi:10.3762/bjnano.10.175

• were recorded using a Leica TCS-SPE CLSM (Leica, Munich, Germany). ROS production in cells treated with AgNPs and AuNPs was determined by the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. DCFH-DA is a non-fluorescent dye that can freely permeate the cell membrane. Inside the cell, it

Novel hollow titanium dioxide nanospheres with antimicrobial activity against resistant bacteria

• Carol López de Dicastillo,
• Cristian Patiño,
• María José Galotto,
• Yesseny Vásquez-Martínez,
• Claudia Torrent,
• Daniela Alburquenque,
• Alejandro Pereira and
• Juan Escrig

Beilstein J. Nanotechnol. 2019, 10, 1716–1725, doi:10.3762/bjnano.10.167

• cells through various processes, such as lipid peroxidation of cell membrane, damaging DNA and/or amino acid- and protein-based cell oxidation [50][51]. This analysis also evidenced that, although an important enhancement of CSTiO2 antimicrobial activity occurred within 60 min of UV irradiation, no

Materials nanoarchitectonics at two-dimensional liquid interfaces

• Katsuhiko Ariga,
• Michio Matsumoto,
• Taizo Mori and
• Lok Kumar Shrestha

Beilstein J. Nanotechnol. 2019, 10, 1559–1587, doi:10.3762/bjnano.10.153

• at interfaces including cell membrane surfaces, inner surfaces of receptor pockets in enzymes, and macromolecular interfaces of DNA. We expect materials nanoarchitectonics with features of enhanced molecular interactions to create low-dimensional materials at interfaces of two phases with different

Scavenging of reactive oxygen species by phenolic compound-modified maghemite nanoparticles

• Małgorzata Świętek,
• Yi-Chin Lu,
• Rafał Konefał,
• Liliana P. Ferreira,
• M. Margarida Cruz,
• Yunn-Hwa Ma and
• Daniel Horák

Beilstein J. Nanotechnol. 2019, 10, 1073–1088, doi:10.3762/bjnano.10.108

• on the cell membrane [32][33]. Particles with phenolic modification further increased the MNPcell value to 1.7- to 2.2-fold and 1.4- to 2.1-fold greater values in L-929 and LN-229 cells, respectively, compared to that of γ-Fe2O3@Hep. These results indicated that phenolic modification may further

• augment particle internalization compared to heparin modification alone. Previous studies have suggested that electrostatic interactions, oxidation-dependent conjugation, and hydrogen bonds between the phenolic OH groups and polysaccharide moieties and/or amino acid residues of the cell membrane may

Correlation of surface-enhanced Raman scattering (SERS) with the surface density of gold nanoparticles: evaluation of the critical number of SERS tags for a detectable signal

• Vincenzo Amendola

Beilstein J. Nanotechnol. 2019, 10, 1016–1023, doi:10.3762/bjnano.10.102

• immunosorbent assay (ELISA) tests, but the analyte may also be naturally immobilized on a surface, such as an antigen overexpressed in cancerous cell membrane [20][21][22]. SERS labels are also useful to probe the uptake of nanomaterial inside living cells [23][24][25][26]. There are many advantages connected

Serum type and concentration both affect the protein-corona composition of PLGA nanoparticles

• Katrin Partikel,
• Robin Korte,
• Dennis Mulac,
• Hans-Ulrich Humpf and
• Klaus Langer

Beilstein J. Nanotechnol. 2019, 10, 1002–1015, doi:10.3762/bjnano.10.101

• lower zeta potential after exposure to serum indicated higher levels of cationic proteins in the corona (Figure 4) [28]. Therefore, we suppose a higher electrostatic attraction between the negatively charged cell membrane and the preincubated PLGA NPs [38]. Moreover, it became apparent that not only the

• that all NP formulations are strongly attached to the cell membranes because they could not be removed by repetitive washings steps during sample processing. As can be seen in Figure 8F, lots of red dots are precisely located in the cell membrane indicating that treatment with PLGA NPs leads to an