Nanomedicines against Chagas disease: a critical review

• Maria Jose Morilla,
• Kajal Ghosal and
• Eder Lilia Romero

Beilstein J. Nanotechnol. 2024, 15, 333–349, doi:10.3762/bjnano.15.30

• in inflamed tissues and could be delivered to amastigotes after being endocytosed by infected cells. In addition, since endocytosis occurs with cellular energy expenditure, the internalization of BNZ would be independent of its permeability and dose. In this way, very small doses of BNZ could be site

Nanocarrier systems loaded with IR780, iron oxide nanoparticles and chlorambucil for cancer theragnostics

• Phuong-Thao Dang-Luong,
• Hong-Phuc Nguyen,
• Loc Le-Tuan,
• Xuan-Thang Cao,
• Vy Tran-Anh and
• Hieu Vu Quang

Beilstein J. Nanotechnol. 2024, 15, 180–189, doi:10.3762/bjnano.15.17

• and F127@NP had the same impact. However, both NPs produced superior outcomes than those for PVA@NP control. It has been demonstrated that F127 can enhance the cellular uptake of NPs in vitro via clathrin-mediated endocytosis and caveolae-mediated endocytosis [31][40]. The absorption of F127 onto

Curcumin-loaded nanostructured systems for treatment of leishmaniasis: a review

• Douglas Dourado,
• Thayse Silva Medeiros,
• Éverton do Nascimento Alencar,
• Edijane Matos Sales and
• Fábio Rocha Formiga

Beilstein J. Nanotechnol. 2024, 15, 37–50, doi:10.3762/bjnano.15.4

• , the in vivo uptake study indicated that the endocytosis of the NPs effectively occurred within macrophages of the reticuloendothelial system. Moreover, in another work of the research group, the authors evaluated the in vitro and in vivo leishmanicidal efficacy and toxicity of these nanoparticles [105

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

• increased albumin endocytosis and a greater uptake of curcumin bound to it into cancer cells [49][50]. Consequently, the use of CUR-HSA-MPs may be a more effective strategy than the use of free CUR for the treatment of cancer. Cell uptake Flow cytometry was employed for the quantitative determination of the

• 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

Prediction of cytotoxicity of heavy metals adsorbed on nano-TiO₂ with periodic table descriptors using machine learning approaches

• Joyita Roy,
• Souvik Pore and
• Kunal Roy

Beilstein J. Nanotechnol. 2023, 14, 939–950, doi:10.3762/bjnano.14.77

• manufactured nanoparticles [39] (Figure 6). Electronegativity and atomic radius influence the catalytic properties of the metal. Metal cations also catalyze the lipid peroxidation process [40] through enhancement of endocytosis and the intrinsic properties of the heavy metal. The toxicity is associated with

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

• nanoformulation provided site-specific delivery via receptor-mediated endocytosis and inhibited proliferation and metastasis in tumors that expressed a specific tumor antigen. The use of adaptor molecules to functionalize antibodies resulted in a highly stable conjugation with improved therapeutic efficacy [69

• smaller when proteins were bound to NPs [81]. Xiao et al. functionalized Tf onto the surface of PEGylated polystyrene NPs to evaluate the effect of the protein corona on blood–brain barrier transcytosis, endocytosis, and intracellular trafficking. They demonstrated that Tf-NPs completely lost their

Nanostructured lipid carriers containing benznidazole: physicochemical, biopharmaceutical and cellular in vitro studies

• Giuliana Muraca,
• María Esperanza Ruiz,
• Rocío C. Gambaro,
• Sebastián Scioli-Montoto,
• María Laura Sbaraglini,
• Gisel Padula,
• José Sebastián Cisneros,
• Cecilia Yamil Chain,
• Vera A. Álvarez,
• Cristián Huck-Iriart,
• Guillermo R. Castro,
• María Belén Piñero,
• Matias Ildebrando Marchetto,
• Catalina Alba Soto,
• Germán A. Islan and
• Alan Talevi

Beilstein J. Nanotechnol. 2023, 14, 804–818, doi:10.3762/bjnano.14.66

• nanoparticles could accumulate in the site of inflammation delivering the drug in the surroundings of their molecular target. In addition, nanocarriers may pass through the cell membrane via endocytosis to avoid BNZ efflux via the P-glycoprotein efflux pump [14][15][16], thus delivering the drug more

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

• one formulation or the failure of another [15][17][27][28]. Within this context, an essential question is: “how are NPs internalized by cells?” [29]. Several mechanisms of endocytosis have been identified as listed in Table 2 [1]. Conventionally, the significance of an endocytosis pathway for a

• particular type of NP can be measured using pharmacological inhibitors or genetic approaches that knockdown/knockout or transiently block the expression of key proteins involved in endocytosis [30]. Then, changes in NP uptake can be quantified and attributed to the significance of that pathway. Unfortunately

• , upon limiting the function of a certain endocytosis pathway, especially through the use of pharmacological inhibitors, cells can respond to the blockage by overactivating alternative mechanisms that would normally be less relevant [31]. This makes the interpretation of each pathway’s significance more

Overview of mechanism and consequences of endothelial leakiness caused by metal and polymeric nanoparticles

• Magdalena Lasak and
• Karol Ciepluch

Beilstein J. Nanotechnol. 2023, 14, 329–338, doi:10.3762/bjnano.14.28

• transcellular route, NPs enter endothelial cells through endocytosis and are transported intracellularly [24][27][28]. Recently, the existence of specific endothelial cells involved in the transport of NPs has been reported [29]. Kingston et al. demonstrated the presence of specific vascular endothelial cells

• NP interaction with cell membranes in order to eliminate the participation of transcellular transport was also investigated. In fact, TEM micrographs revealed a small number of 18 nm AuNPs undergoing endocytosis. However, subsequent studies with a cocktail of endocytosis inhibitors confirmed the

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

• 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

Supramolecular assembly of pentamidine and polymeric cyclodextrin bimetallic core–shell nanoarchitectures

• Alexandru-Milentie Hada,
• Nina Burduja,
• Marco Abbate,
• Claudio Stagno,
• Guy Caljon,
• Louis Maes,
• Nicola Micale,
• Massimiliano Cordaro,
• Angela Scala,
• Antonino Mazzaglia and
• Anna Piperno

Beilstein J. Nanotechnol. 2022, 13, 1361–1369, doi:10.3762/bjnano.13.112

• structure. In this case, the inner Au component favors cellular entry (typically via endocytosis) and slow release of the Ag+ ions, to which the overall biological activity of the system is ascribed. It all comes down to greater system biocompatibility [2]. Au/Ag BMNPs with a core–shell architecture can be

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

• ]. Contrarily, nanoparticles composed of a lipid bilayer with cores of different crosslinking extent showed higher uptake of softer particles in MCF-7 cells, which was thought to be due to a melting process of particles with the cell membrane that consumed less energy than endocytosis [8]. Regarding the in vivo

Engineered titania nanomaterials in advanced clinical applications

• Padmavati Sahare,
• Paulina Govea Alvarez,
• Juan Manual Sanchez Yanez,
• Gabriel Luna-Bárcenas,
• Samik Chakraborty,
• Sujay Paul and
• Miriam Estevez

Beilstein J. Nanotechnol. 2022, 13, 201–218, doi:10.3762/bjnano.13.15

• -functionalized, or post-synthetically modified by adding various surfactants or dopants or organic molecules. The size of the nanomaterial also determines the type of immune response elicited by the body (endocytosis/cellular uptake) [21]. Xu et al. reported that the size of the pores is an essential parameter

• dendrimer nps as well as inorganic nanoscale drug carriers are currently used for drug delivery [101]. Almost all of them show higher bioavailability as their uptake mechanism is by absorptive endocytosis, and the slow release of drugs in the blood circulatory system efficiently maintains the level of

• . synthesized B-TiO2−x nps by a facile aluminium reduction process and modified its surface with PEG molecules (Figure 7) for high stability under physiological conditions. B-TiO2−x-PEG accumulates in tumor tissue via typical endocytosis processes and functions as nanosonosensitizer as well as photothermal

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

• positively charged PEI electrostatically condenses high molecular weight (MW) DNA to polypeptic nanoparticles (10–100 nm), which are capable of being absorbed by endocytosis [50][51]. Usually, the main purpose of using PEI coating on SPIONs is to provide cationic nanoparticles suitable for gene binding and

• polypeptic nanoparticles (10–100 nm), which are capable of being absorbed by endocytosis [50][51]. The gel retardation of poly I:C (dsRNA analogue) happens after interacting with positively charged nanoparticles. According to our gel electrophoresis results and comparing between free poly I:C (well 8), at an

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

• . Results showed that cells readily internalized MNP by endocytosis, which simultaneously allowed for imaging the affected cells [132]. Other report showed that, using the same breast cancer cells, alginate/chitosan MNP had a 3–6-fold increase in cellular uptake, as compared to F-CUR [133]. This has been

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

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

• ]. Early reports in the field of ultrasonic drug delivery demonstrated that the application of US energy alone could facilitate intracellular delivery of molecules by altering membrane integrity or interfering with the endocytosis process; however, this could also be harmful to the cells under some

• cytoplasm through simple diffusion. Moreover, these stresses can activate cellular stress signaling pathways [83]. Previous studies have concluded that two mechanisms could be involved in US-mediated drug delivery and cell uptake of impermeable molecules: sonoporation and increased endocytosis [84][85

• ]. However, a few studies have demonstrated that the endocytosis pathway is the main mechanism for the delivery of large molecules mediated by US [33][84][85]. Schlicher et al. investigated the uptake and transfer of different molecular weight fluorescent molecules, including calcein, fluorescein

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

• vesicles, and phagosomes could be employed as a gateway for endocytosis-mediated transcellular transport across the MBB [19]. Since there is no lymphatic drainage, the BM tissue relies on these pathways for bidirectional transport of a variety of molecules across the MBB. The capability of the sinusoidal

• 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

• receptor-mediated endocytosis, that carry several functional agents against multiple intracellular pathways or different components of the EGFR signaling network. The systems are (i) nanoscale systems capable of downregulation or inhibition of positively correlated receptors in order to improve the

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

• imaging techniques. The results revealed that the route of MNP entry into cells strongly depends on the surface chemistry of the MNPs. While serum bovine albumin-coated MNPs entered the cells via clathrin-mediated endocytosis (CME), caveolin-mediated endocytosis (CavME) or lipid rafts were preferentially

• nanoparticles is one of the critical steps during the development of new nanotechnology-based pharmaceuticals. Nanoparticles can enter the cell through various specific and non-specific pathways of endocytosis, divided into two broad categories, that is, phagocytosis and pinocytosis [7]. While phagocytosis

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

• endocytosis of nanotubes. Three kinds of CNTs-COOH samples, produced using different acid solutions, are all dispersed into single tubes with smooth surface without aggregation, and no obvious difference in the morphological characteristics is observed (Figure 2B–D, Figure 3B–D). The tubular structure of CNTs

• difference between the pH values of healthy blood and of tumor cells where the CNT carriers accumulate after endocytosis, especially in endosomes and lysosomes, this pH-dependent release will benefit the expected antitumor treatment. CNTs-PEG-PEI/DOX remains relatively stable when circulating in normal

• molecules enter cells only by mobility or diffusion, while the individually dispersed nanotubes are more easily internalized by cells via direct penetration and endocytosis [38][43]. This can explain the above results. The fluorescence intensity of CNTs-PEG/DOX and CNTs-PEG-PEI/DOX increases further (Figure

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

• degradation by facilitating the release of the gene into the cytoplasm. Endocytosis has been well known as the main mechanism for cellular uptake of nanoparticles into mammalian cells [13][14]. The endocytosis process encompasses four main routes [15]: phagocytosis, clathrin-mediated endocytosis, caveolae

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

• therapeutic efficacy, and safety studies. Keywords: drug delivery; drug targeting; endocytosis; medical; nanoparticles; superparamagnetic iron oxide nanoparticles (SPIONs); toxicity; Introduction Nanoencapsulation technologies have been researched over the past several decades and have been widely

• reticuloendothelial system [85][96]. Hennig et al. [97] obtained lauric acid/BSA-coated and dextran-coated SPIONs with neutral surface charge, which remained colloidally stable without forming any aggregates. This feature is very important for cell endocytosis, as aggregates precipitate between cells in vitro and

• readily detected. Figure 3 gives a schematic overview of how the physical and chemical characteristics of SPIONs influence biological response and biomedical applications. Endocytosis, exocytosis, retention and clearance There are a number of possible cell entry mechanisms for nanoparticles, such as

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

• [39]. However, this pathway remains one of the most promising for drug delivery through the BBB. Transcytosis includes three steps: endocytosis, intracellular vesicular trafficking and exocytosis [40]. Indeed, molecules bind to their receptors on the luminal side of the endothelial cells and

• endocytosis is initiated. The receptor–ligand complex is invaginated, which leads to the formation of intracellular transport vesicles. The vesicles are then sorted and the ones sorted for exocytosis cross the cell to release the ligand to its basolateral side. The receptor is then recycled [41]. Some of the

• 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

Luminescent gold nanoclusters for bioimaging applications

• Nonappa

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

• endocytosis. The superparamagnetic nature of the PML-MF allowed for the magnetic targeting of the nanocarriers. Further, the ability of BSA to encapsulate drug molecules was explored to load doxorubicin (DPML-MF) in the nanocarriers. The release kinetics of doxorubicin studied at pH 7.4 and 4.4 were found to

• endocytosis of NCs. The generation of ROS upon X-ray irradiation in the presence of [Au8(C21H27O2)8] significantly suppressed the tumorigenicity in vivo after one radiotherapy treatment in mouse models. Because of their well-defined surface functionalities and small size, the dispersion behavior of NCs is

• the rational design of nanocarriers encapsulating poorly soluble drugs for targeted delivery. Cell line-based studies have provided enough evidence that the internalization of AuNCs occurs through endocytosis. However, there are several challenges to utilize AuNCs in bacterial sensing due to their

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

• . These results differ from those reported for cell internalization of cowpea mosaic virus (CPMV) in the same cell lines, which do not show high levels of vimentin on the cell surface [20][34]. Vimentin is a receptor that facilitates caveolar endocytosis [35][36], and it has been reported to promote the

• cellular internalization of CPMV [32][35][36][37]. Therefore, the cellular internalization of the CPMV virus occurs via endocytosis, which includes multiple routes: clathrin-dependent, caveolar and micropinocytosis [36][37][38]. Our results showed that the presence of low levels of vimentin on the cell