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

Molecular architectonics of DNA for functional nanoarchitectures

• Debasis Ghosh,
• Lakshmi P. Datta and
• Thimmaiah Govindaraju

Beilstein J. Nanotechnol. 2020, 11, 124–140, doi:10.3762/bjnano.11.11

• altered the FRET response, which was exploited for sensing of acidic pH (3–5.5) with a low step size (0.2–0.3) within synthetic vesicles that mimicked the intracellular environment. The in cellulo study in HeLa cells demonstrated the efficient cellular uptake of the DNA device without the need for a

• scaffolds to construct and modulate structural and functional patterns. The tetrahedron with regular edges and acmes is a perfect architectural shape for the construction of DNA nanoarchitectures. The virus-mimetic feature of the DNA tetrahedron accounts for the facile cellular uptake via a caveolin

• oligonucleotide sequences, DNA tiles were also used to build DNA tetrahedrons. In another approach, DNA tetrahedron cages were prepared for efficient cellular uptake and imaging of live cells [67]. Human embryonic kidney (HEK) cells were cultured with a range of fluorescently tagged DNA tetrahedrons, and 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

• are dethroning small molecules as leading therapeutics. Given their immense potential, they are highly sought after. However, their application is limited mostly due to their poor in vivo stability, limited cellular uptake and insufficient target specificity. Cell-penetrating peptides (CPPs) represent

• 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

• number of diseases render them exceptionally attractive. Nonetheless, there are some obstacles that need to be overcome, such as the limited cellular uptake and low target specificity of these molecules. In order to do so, we are in great need for new delivery and administration strategies. Thus far, a

The different ways to chitosan/hyaluronic acid nanoparticles: templated vs direct complexation. Influence of particle preparation on morphology, cell uptake and silencing efficiency

• Arianna Gennari,
• Julio M. Rios de la Rosa,
• Erwin Hohn,
• Maria Pelliccia,
• Enrique Lallana,
• Roberto Donno,
• Annalisa Tirella and
• Nicola Tirelli

Beilstein J. Nanotechnol. 2019, 10, 2594–2608, doi:10.3762/bjnano.10.250

• significant. B) The cellular uptake of nanoparticles was followed by measuring the fluorescence of lysates after cells were incubated with particles containing RITC-labelled chitosan or rhodamine-labelled HA. The lysate fluorescence is a quantitative measure of the nanoparticle uptake (bound and internalized

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

• on the ability of functional fusion proteins presenting a lytic gamma peptide, to promote interactions with HeLa cells and delivery of large hybrid nanostructures. Keywords: bioconjugation; cellular uptake; nanoparticle hybrids; polymer encapsulation; self-assembly; Introduction Developing hybrid

• stability and tumour accumulation of curcumin [17]. Overall, there is a consensus that using colloidally stable nanoparticles is crucial for understanding and controlling cellular uptake, because materials that are prone to aggregation show higher non-specific interactions with biological fluids and cell

• incubated with nanohybrids prepared with His6-MBP-γ yielded pronounced intracellular staining; the control cultures did not show any cellular uptake (see Figure 1D and Figures S3 and S4 in Supporting Information File 1). In addition, the distribution of the QD staining (shown in Figure 1E, top panels) is

pH-Controlled fluorescence switching in water-dispersed polymer brushes grafted to modified boron nitride nanotubes for cellular imaging

• Saban Kalay,
• Yurij Stetsyshyn,
• Volodymyr Donchak,
• Khrystyna Harhay,
• Ostap Lishchynskyi,
• Halyna Ohar,
• Yuriy Panchenko,
• Stanislav Voronov and
• Mustafa Çulha

Beilstein J. Nanotechnol. 2019, 10, 2428–2439, doi:10.3762/bjnano.10.233

• used in cellular uptake studies. The cells were imaged with a Zeiss Axio Imager.M2 instrument at an excitation wavelength of 490 nm and emission of 520 nm. Results and Discussion Fabrication and properties of fluorescent boron nitride nanotubes The pH-responsive fluorescent coatings were formed on the

• BNNTs clearly showed fluorescence not only in the nuclei but also in the cytosol. The reason for this is likely due to the more internalized material compared to the healthy cells as a result of higher metabolic activity of cancer cells. This study clearly shows that the cellular uptake of P(AA-co-FA

Incorporation of doxorubicin in different polymer nanoparticles and their anticancer activity

• Sebastian Pieper,
• Hannah Onafuye,
• Dennis Mulac,
• Jindrich Cinatl Jr.,
• Mark N. Wass,
• Martin Michaelis and
• Klaus Langer

Beilstein J. Nanotechnol. 2019, 10, 2062–2072, doi:10.3762/bjnano.10.201

• . It is the only preparation in which nanoparticles have a size clearly smaller than 100 nm (72.6 ± 3.3 nm, Figure 1). This might indicate that the cellular uptake of smaller nanoparticles is higher than that of larger nanoparticles, which is coherent with previous findings showing that cellular uptake

• shown to bypass efflux-mediated drug resistance [25]. This included various nanoparticle and liposome formulations of the ABCB1 substrate doxorubicin that were shown to modify the cellular uptake and intracellular distribution of doxorubicin resulting in enhanced effects against ABCB1-expressing cancer

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) for dual-modality imaging of intracranial glioblastoma via EGFRvIII targeting

• Xianping Liu,
• Chengjuan Du,
• Haichun Li,
• Ting Jiang,
• Zimiao Luo,
• Zhiqing Pang,
• Daoying Geng and
• Jun Zhang

Beilstein J. Nanotechnol. 2019, 10, 1860–1872, doi:10.3762/bjnano.10.181

• centrifugation was performed at 1000 rpm for 4 min. Finally, 0.5 mL of PBS (0.01 M, pH 7.4) was used to suspend the cells and the fluorescence intensity of the cells was ascertained by flow cytometry (BD, USA). Cellular uptake of PEG-SPIONs The cellular uptake of NPs and PNPs were investigated on U87MG and U87MG

• qualitative analysis, the cells were washed with PBS (0.01 M, pH 7.4) three times, then DAPI-stained and observed under a fluorescence microscope (Leica, DMI4000B, Germany). For the quantitative examination of the cellular uptake of the nanoprobes, U87MG and U87MG-EGFRvIII cells were harvested after trypsin

• -EGFRvIII cells. Cellular uptake of PNPs by U87MG-EGFRvIII cells To demonstrate the targeting ability of PNPs, in vitro cellular uptake of PNPs was investigated by U87MG-EGFRvIII cells. After incubation with NPs and PNPs for 2 h, the fluorescence intensity of U87MG-EGFRvIII cells in the PNP group was

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

• [87]. The reflection contrast mode of CLSM, as excellent non-invasive imaging strategy for label-free real-time tracking and quantification of non-fluorescent NPs [88], was used to visualize cellular uptake of NPs. In brief, the cells were grown in a 12-well chamber with glass slides (Eppendorf

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

• -diphenyl-1-picrylhydrazyl (DPPH) assay. Cellular uptake and intracellular antioxidant activity of the particles were evaluated by an iron assay and flow cytometry, respectively, using L-929 and LN-229 cells. Compared to the control, the phenolic modification significantly reduced intracellular reactive

• oxygen species (ROS) levels to 35–56%, which was associated with a 6–8-times higher cellular uptake in L-929 cells and a 21–31-times higher cellular uptake in LN-229 cells. In contrast, γ-Fe2O3@Hep particles induced a 3.8-times and 14.9-times higher cellular uptake without inducing antioxidant activity

• . In conclusion, the high cellular uptake and the antioxidant properties associated with the phenolic moieties in the modified particles allow for a potential application in biomedical areas. Keywords: antioxidants; chitosan; maghemite nanoparticles; oxidative stress; phenolic compound; Introduction

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

• for the biological response in terms of body biodistribution, cellular uptake, and toxicity. The corona is dynamic in nature and it is well known that the composition varies in dependence of the physicochemical properties of the NPs. In the present study we investigated the protein corona that forms

• of NPs forming a protein corona [4]. Consequently, the synthetic identity of the NPs is replaced by a new biological identity that determines their physiological response including biodistribution, cellular uptake, trafficking, and toxicity [5]. Corona formation is a very dynamic process in nature

Effects of gold and PCL- or PLLA-coated silica nanoparticles on brain endothelial cells and the blood–brain barrier

• Aniela Bittner,
• Angélique D. Ducray,
• Hans Rudolf Widmer,
• Michael H. Stoffel and
• Meike Mevissen

Beilstein J. Nanotechnol. 2019, 10, 941–954, doi:10.3762/bjnano.10.95

• physicochemical properties, the formation of NP clusters before entry into the cell may modulate the cellular uptake [9][34]. NPs might not only cause cytotoxicity but also hinder proliferation, differentiation or lead to inflammation via activation or inhibition of various pathways including phosphatidylinositol

Polydopamine-coated Au nanorods for targeted fluorescent cell imaging and photothermal therapy

• Boris N. Khlebtsov,
• Andrey M. Burov,
• Timofey E. Pylaev and
• Nikolai G. Khlebtsov

Beilstein J. Nanotechnol. 2019, 10, 794–803, doi:10.3762/bjnano.10.79

• ) loading, resulting in the formation of AuNR-PDA-R123-folate nanocomposites (Scheme 1). This platform demonstrates three distinct features: (1) targeting of nanocomposites with folic acid leads to enhanced cellular uptake by folate-positive cancer cells compared with PEG-coated nanorods; (2) the high

• -light illumination due to the presence of R123 molecules. Additionally, nanoparticles can selectively accumulate in the cancer cells because of targeting to folate receptors. Folate-mediated cell imaging Efficient cellular uptake of nanocarriers is significant to ensure the therapeutic efficacy of

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

• cellular targeting moieties on the nanocarrier surface. Through tissular targeting the nanocarrier would be directed to the diseased cells improving its accumulation. Once there, the presence of the cellular targeting moieties would enhance the cellular uptake into the tumoral cells. In several types of

Surface plasmon resonance enhancement of photoluminescence intensity and bioimaging application of gold nanorod@CdSe/ZnS quantum dots

• Siyi Hu,
• Yu Ren,
• Yue Wang,
• Jinhua Li,
• Junle Qu,
• Liwei Liu,
• Hanbin Ma and
• Yuguo Tang

Beilstein J. Nanotechnol. 2019, 10, 22–31, doi:10.3762/bjnano.10.3

• @CdSe/ZnS can be used in cell imaging studies, after conjugation with FA, we performed a MCF-7 breast cancer cell targeting imaging study, and the results as shown in Figure 8. Robust cellular uptake could be obtained from the CdSe/ZnS@FA and GNR@CdSe/ZnS@FA treated samples. The obvious luminescence and

The nanoscaled metal-organic framework ICR-2 as a carrier of porphyrins for photodynamic therapy

• Jan Hynek,
• Sebastian Jurík,
• Martina Koncošová,
• Jaroslav Zelenka,
• Ivana Křížová,
• Tomáš Ruml,
• Kaplan Kirakci,
• Ivo Jakubec,
• František Kovanda,
• Kamil Lang and
• Jan Demel

Beilstein J. Nanotechnol. 2018, 9, 2960–2967, doi:10.3762/bjnano.9.275

• substituent at the porphyrin phosphinate groups. Thus, phosphinatophenylporphyrin with phenyl substituents has the strongest photodynamic efficacy due to the most efficient cellular uptake. Keywords: metal-organic framework; phosphinic acid based MOF; photodynamic therapy; porphyrin; singlet oxygen

• the proximity of iron atoms constituting the ICR-2 structure. It is worth noting that the porphyrin loading does not affect the fluorescence quantum yields. Photobiological properties Cellular uptake and intracellular localization HeLa cells were treated with the nanoparticles in Eagle's Minimum

• Essential Medium (EMEM) without foetal bovine serum to avoid modification of the particle surface properties by nonspecific binding of serum albumin. The cellular uptake of the nanoparticles was quantified by flow-cytometry analysis of porphyrin fluorescence associated with the cells. Figure 6A shows the

Cytotoxicity of doxorubicin-conjugated poly[N-(2-hydroxypropyl)methacrylamide]-modified γ-Fe₂O₃ nanoparticles towards human tumor cells

• Zdeněk Plichta,
• Yulia Kozak,
• Rostyslav Panchuk,
• Viktoria Sokolova,
• Matthias Epple,
• Lesya Kobylinska,
• Pavla Jendelová and
• Daniel Horák

Beilstein J. Nanotechnol. 2018, 9, 2533–2545, doi:10.3762/bjnano.9.236

• undifferentiated cells, mesenchymal stem cells were utilized. Cellular uptake of agents was studied by fluorescence microscopy and induction of cell death was visualized by live/dead assay. Dox-conjugated γ-Fe2O3@P(HPMA-MMAA) particles showed enhanced cytotoxicity in drug-sensitive and drug-resistant tumor cells

• attached to the cells. The cellular uptake was measured by fluorescence microscopy with a Keyence Biorevo BZ-9000 instrument (Osaka, Japan) equipped with filters for Texas Red (EX 560/40, DM 585, BA 630/75) at 20× magnification. Dox and its complexes were visible as red fluorescing dots. Live/dead assay

• their enhanced accumulation inside the cells. The particles are able to penetrate cells by the selected type of endocytosis mechanism: phagocytosis, pinocytosis, or receptor mediated endocytosis [25]. In order to check this hypothesis, cellular uptake of γ-Fe2O3@P(HPMA-MMAA)-Dox nanoparticles was

Enhanced antineoplastic/therapeutic efficacy using 5-fluorouracil-loaded calcium phosphate nanoparticles

• Shanid Mohiyuddin,
• Saba Naqvi and
• Gopinath Packirisamy

Beilstein J. Nanotechnol. 2018, 9, 2499–2515, doi:10.3762/bjnano.9.233

• with 5-FU and resulted in enhanced cellular uptake and efficacy [18]. Furthermore, a chitosan/gold nanocomposite was employed as a load carrier for 5-FU with an encapsulation efficiency of 96% [19]. Interestingly, monomeric self-assembled nucleoside nanoparticles (SNNPs) loaded with 5-FU were shown to

• agglomeration and enhanced colloidal stability [29]. Since the particle stability mainly depends on the electrical charge of the surface, properties such as cellular uptake, rate of drug release, and blood retention time are directly correlated with the zeta potential value. Furthermore, the zeta potential

• showed a concentration-dependent toxicity on the cells irrespective of the cell lines used. In NIH 3T3 cells, considerably low toxicity was found (Figure 4A) with respect to cancer cells. The increased metabolism in cancer cells might be the reason for the enhanced cellular uptake [39] of the particles

Review on nanoparticles and nanostructured materials: history, sources, toxicity and regulations

• Jaison Jeevanandam,
• Ahmed Barhoum,
• Yen S. Chan,
• Alain Dufresne and
• Michael K. Danquah

Beilstein J. Nanotechnol. 2018, 9, 1050–1074, doi:10.3762/bjnano.9.98

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

• observed between the absolute value of the zeta potential and the cellular uptake observed in both LN-229 and HK-2 cells. XRD patterns of the four synthesized C-dots have been also studied, and the obtained results are given in Figure 5. The cinnamon, red chilli, turmeric and black pepper C-dots

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

• treated with endocytotic inhibitors recovered after co-exposure, which additionally hinted that two uptake mechanisms are involved. Cross-talk between uptake pathways is relevant for toxicological studies: Co-exposure acts as an uptake accelerant. If the goal is to maximize the cellular uptake, e.g., for

• the effects of exposure to each individual NP [26]. Moreover, little is known about how co-exposure of different NPs affects cellular uptake (e.g., whether it enhances or even inhibits selective NP uptake), which is –particularly in nanomedicine– highly relevant to the understanding of their behaviour

• in a complex colloidal system, such as the vascular system. The aim of this work was to study the combined effect of two model NPs on cellular uptake, that is gold (AuNPs) and iron oxide NPs (FeOxNPs) stabilized with the same polymer shell and incorporated fluorophores. The NPs can be distinguished

Carbon nano-onions as fluorescent on/off modulated nanoprobes for diagnostics

• Stefania Lettieri,
• Marta d’Amora,
• Adalberto Camisasca,
• Alberto Diaspro and
• Silvia Giordani

Beilstein J. Nanotechnol. 2017, 8, 1878–1888, doi:10.3762/bjnano.8.188

• development of a nanosensor which can be “turned on” in an acidic environment. Remarkably, the fluo-CNOs maintained the switching properties upon cell internalization, as they were “switched-on” in response to acidic pH. In vitro experiments on HeLa cells showed excellent cellular uptake and low toxicity of

• fluo-CNOs were successfully internalized by cells and were distributed throughout the cytoplasm. Remarkably the cellular uptake of the fluo-CNOs was clearly observed soon after the incubation, as shown by the presence of CNOs inside the cell after 2 h (Figure 8A). After 12 and 48 h of incubation

• 1 h, pH 4.5; Scale bars = 20 μm. Cellular uptake and localization of fluo-CNOs in HeLa cells in acidic conditions (PBS, pH 4.5) observed by confocal fluorescence microscopy after incubation for 2 h (A), 12 h (B) and 48 h (C), respectively. Scale bars = 20 μm. Three-dimensional reconstruction by

Development of polycationic amphiphilic cyclodextrin nanoparticles for anticancer drug delivery

• Gamze Varan,
• Juan M. Benito,
• Carmen Ortiz Mellet and
• Erem Bilensoy

Beilstein J. Nanotechnol. 2017, 8, 1457–1468, doi:10.3762/bjnano.8.145

• particle size of nanoparticulate drug delivery systems play a direct and important role on cellular uptake, systemic circulation, toxicity and stability of nanoparticles [37][38]. It was reported that nanoparticles smaller than 200 nm can escape recognition by the mononuclear phagocytic system (MPS) [39

• negatively charged molecules (e.g., sialic acid, cholesterol, phospholipid) on cell membrane easier than anionic nanoparticles [26][52]. In addition, the surface charge of nanoparticles play an important role on cellular uptake and subcellular localization [53][54]. Another reason for the cell viability

Cationic PEGylated polycaprolactone nanoparticles carrying post-operation docetaxel for glioma treatment

• Cem Varan and
• Erem Bilensoy

Beilstein J. Nanotechnol. 2017, 8, 1446–1456, doi:10.3762/bjnano.8.144

• agents to the tumor site, while avoiding possible side effects. The development of novel drug delivery systems with reduced side effects is an important breakthrough and nanoparticles are promising in this field as they enable localized drug delivery to target sites and enhanced cellular uptake

• –shell PCL nanoparticles to tumor targeting with docetaxel on a glioma model is very rare. Recently, active-targeted docetaxel-loaded PEG/PCL nanoparticles were prepared successfully for glioblastoma therapy by Gao et al. Cellular uptake and tumor spheroid uptake studies on U87 human glioma cells show

• obtained by dual drug targeting. Besides that, the magnetic and ligand targeting resulted in elevated cellular uptake of nanocapsules in glioma treatment [26]. Yang et al. successfully obtained targeted and traceable core–shell nanoparticles for carmustine (BCNU) delivery. These systems prolonged the half

Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation

• Kati Erdmann,
• Jessica Ringel,
• Silke Hampel,
• Manfred P. Wirth and
• Susanne Fuessel

Beilstein J. Nanotechnol. 2017, 8, 1307–1317, doi:10.3762/bjnano.8.132

• S1c,d) [28]. Consistently, the reduction of the chemotherapeutic dosage was more distinct in combinatory treatments with CNFs independent of the chemotherapeutic used. A combined application with carbon nanomaterials would also result in an improved cellular uptake of the active drug component as