Development of a mucoadhesive drug delivery system and its interaction with gastric cells

• Ahmet Baki Sahin,
• Serdar Karakurt and
• Deniz Sezlev Bilecen

Beilstein J. Nanotechnol. 2025, 16, 371–384, doi:10.3762/bjnano.16.28

• nanoparticles is a dynamic process where both endocytosis and exocytosis are involved. The uptake also depends on the concentration of nanoparticles and the duration of the process. Studies conducted with the AGS cell line revealed that nanoparticle internalization generally reaches a plateau within the first 2

Graphene oxide–chloroquine conjugate induces DNA damage in A549 lung cancer cells through autophagy modulation

• Braham Dutt Arya,
• Sandeep Mittal,
• Prachi Joshi,
• Alok Kumar Pandey,
• Jaime E. Ramirez-Vick,
• Govind Gupta and
• Surinder P. Singh

Beilstein J. Nanotechnol. 2025, 16, 316–332, doi:10.3762/bjnano.16.24

• hydrophobicity, and C/O ratio) GO is internalized via clathrin or caveolae-mediated endocytosis and micropinocytosis [53]. The exposure to nanomaterials is known to affect plasma membrane integrity, which in turn initiates various metabolic processes, such as ineffective nutrient transport, unspecific molecular

Radiosensitizing properties of dual-functionalized carbon nanostructures loaded with temozolomide

• Radmila Milenkovska,
• Nikola Geskovski,
• Dushko Shalabalija,
• Ljubica Mihailova,
• Petre Makreski,
• Dushko Lukarski,
• Igor Stojkovski,
• Maja Simonoska Crcarevska and
• Kristina Mladenovska

Beilstein J. Nanotechnol. 2025, 16, 229–251, doi:10.3762/bjnano.16.18

• ) and caveolin-mediated endocytosis (GO with diameter below 100 nm). In addition, accumulation in the glia cells due to the enhanced permeability and retention effect was observed. However, it is emphasized that surface modification, including modification of surface charge and particle size, can

Nanocarriers and macrophage interaction: from a potential hurdle to an alternative therapeutic strategy

• Naths Grazia Sukubo,
• Paolo Bigini and
• Annalisa Morelli

Beilstein J. Nanotechnol. 2025, 16, 97–118, doi:10.3762/bjnano.16.10

• in KCs, is essential for clearing infections caused by the Gram-positive bacterium Listeria monocytogenes [30]. In nanomedicine, SRs are also responsible for clearing negatively charged NPs such as those composed of silica [31][32]. This interaction leads to the internalization of NCs via endocytosis

• demonstrated by Ji and colleagues in a mouse model of carbon tetrachloride (CCl4)-induced fibrosis, where they inhibited the proliferation of fibroblasts [46]. An alternative to depletion is the inhibition of KCs through chloroquine, an antimalaria agent that inhibits macrophage-specific endocytosis, or

• final effect. Endocytosis poses a significant challenge for delivering drugs and nucleic acids to the cytosol as most remain trapped in endosomes and subsequently degrade. Efficient delivery requires the payload to be released before lysosomal maturation, a crucial stage known as endosomal escape [53

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

• transforming drug delivery methodologies [1]. Despite their potential, liposomes encounter substantial challenges from the point of administration to achieving therapeutic efficacy. One of the primary obstacles is their propensity for endosomal entrapment. Following internalization via endocytosis, liposomes

• was investigated using different endocytic pathway inhibitors (Figure 2). For Unmodified-Lipo (Figure 2a,d), sucrose, which inhibits clathrin-mediated endocytosis, significantly reduced fluorescence intensity (p < 0.001), indicating that clathrin-mediated endocytosis is a primary pathway. Filipin, an

• 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

Polymer lipid hybrid nanoparticles for phytochemical delivery: challenges, progress, and future prospects

• Iqra Rahat,
• Pooja Yadav,
• Aditi Singhal,
• Mohammad Fareed,
• Jaganathan Raja Purushothaman,
• Mohammed Aslam,
• Raju Balaji,
• Sonali Patil-Shinde and
• Md. Rizwanullah

Beilstein J. Nanotechnol. 2024, 15, 1473–1497, doi:10.3762/bjnano.15.118

• and synergistic therapeutic efficacy against breast cancer (BC) [63]. The scheme for the development of these ligand-decorated PLHNPs is depicted in Figure 3. The findings suggested that the targeted PLHNPs significantly improved uptake in BC cells by receptor-mediated endocytosis when compared with

• endocytosis. IQN-iRGD-PLHNPs also exhibited much higher cytotoxicity than non-targeted IQN-PLHNPs and free IQN. Interestingly, after leveraging iRGD peptides for active tumor-tissue accumulation and employing a stealth nanostructure for prolonged in vivo circulation, ISL-iRGD NPs exhibited superior

• profiles. The cell culture studies indicated that the targeted PLHNPs showed much greater cell uptake in MDA-MB-435s cells by integrin receptor-medicated endocytosis than the non-targeted PLHNPs. The targeted PLHNPs showed a significant reduction in IC50 value (by ≈50%) compared to the non-targeted PLHNPs

Nanotechnological approaches for efficient N2B delivery: from small-molecule drugs to biopharmaceuticals

• Selin Akpinar Adscheid,
• Akif E. Türeli,
• Nazende Günday-Türeli and
• Marc Schneider

Beilstein J. Nanotechnol. 2024, 15, 1400–1414, doi:10.3762/bjnano.15.113

• [67][68]. Significant portions of the NPs studied for N2B delivery are approx. 200 nm, which is the average size of olfactory exons [44][60]. Rejman et al. demonstrated that the clathrin-mediated pathway of endocytosis has an upper limit for internalization of approximately 200 nm. Their study also

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

• in the liver [27][28]. The interaction of the nanocarriers with various types of cells is size-dependent [30]. Nanocarriers with a particle size bigger than 100 nm could be taken up by LSECs and Kupffer cells through endocytosis. With the increase of particle size, the uptake of nanocarriers by

• targeting activated HSCs. The presence of HSA on the surface of the nanocrystals may facilitate active targeting to activated HSCs via secreted protein acidic and rich in cysteine (SPRAC)-mediated endocytosis. It was reported that the activated HSCs overexpressed SPRAC, which is known as classic albumin

Unveiling the potential of alginate-based nanomaterials in sensing technology and smart delivery applications

• Shakhzodjon Uzokboev,
• Khojimukhammad Akhmadbekov,
• Ra’no Nuritdinova,
• Salah M. Tawfik and
• Yong-Ill Lee

Beilstein J. Nanotechnol. 2024, 15, 1077–1104, doi:10.3762/bjnano.15.88

• absorbed DOX-loaded UCNP-Al-NH-PEG-NH-FA by FR-mediated endocytosis, which resulted in intracellular pH-triggered DOX release and consequent apoptosis (Figure 3B) [19][47]. Chemically modified derivatives of alginate for DDS Sodium alginate has many carboxylate groups and can be used as a reactive polymer

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

• excretion. Finally, we discuss requirements for bringing NPs into clinical use and aspects when it comes to usage of complex and slowly degraded or nondegradable NPs. Keywords: biodegradable; biodistribution; endocytosis; extracellular vesicles; nanomedicine; nanoparticles; Introduction Nanoparticles (NPs

• Nanoparticle Uptake The complexity of endocytosis The field of endocytosis has undergone a remarkable development during the last decades. Today it is clear that there is a variety of uptake mechanisms in cells, and adding to the complexity, they are partially cell-type specific [7][8][9][10]. In Figure 1, we

• 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

Therapeutic effect of F127-folate@PLGA/CHL/IR780 nanoparticles on folate receptor-expressing cancer cells

• Thi Ngoc Han Pham,
• Phuong-Thao Dang-Luong,
• Hong-Phuc Nguyen,
• Loc Le-Tuan,
• Xuan Thang Cao,
• Thanh-Danh Nguyen,
• Vy Tran Anh and
• Hieu Vu_Quang

Beilstein J. Nanotechnol. 2024, 15, 954–964, doi:10.3762/bjnano.15.78

• of folic acid did not change the level of the cell signal. F127 also assists in the accumulation of the nanoparticles in the cell via clathrin-mediated endocytosis and caveolae-mediated endocytosis [9][44]. In our study, F127 enhanced the internalization of the nanoparticles in MCF7, HepG2, and HEK

• with the binding of F127 nanoparticles. Clathrin-mediated endocytosis and caveolin-mediated endocytosis occur in most of the cells; therefore, the internalization of the nanoparticles to the cell would be unselective [45]. Thus, there were fluorescent signals in the cells, most of which were incubated

• the cell via clathrin-mediated endocytosis and caveolae-mediated pathways. Thus, our nanoparticles have the potential to serve as medication carriers. Besides, it could also be used as an imaging tracer because of the IR780 compound in the nanoparticles. Many studies have encapsulated IR780 in

Cholesterol nanoarchaeosomes for alendronate targeted delivery as an anti-endothelial dysfunction agent

• Horacio Emanuel Jerez,
• Yamila Roxana Simioni,
• Kajal Ghosal,
• Maria Jose Morilla and
• Eder Lilia Romero

Beilstein J. Nanotechnol. 2024, 15, 517–534, doi:10.3762/bjnano.15.46

• (HUVECs) were determined after endocytosis of ALN-loaded nanoarchaeosomes (nanoARC-Chol(ALN), made of polar lipids from Halorubrum tebenquichense: cholesterol 7:3 w/w, 166 ± 5 nm, 0.16 ± 0.02 PDI, −40.8 ± 5.4 mV potential, 84.7 ± 21 µg/mg ALN/total lipids, TL). The effect of nanoARC-Chol(ALN) was further

• basal compartments. The endocytosis of nanoARC-Chol(ALN), was observed to partly reduce the endothelial-mesenchymal transition of HUVECs. Besides, while 10 mg/mL dexamethasone, 7.6 mM free ALN and ALN-loaded liposomes failed, 50 μg/mL TL + 2.5 μg/mL ALN (i.e., nanoARC-Chol(ALN)) reduced the IL-6 and IL

• -8 levels by, respectively, 75% and 65% in the mild and by, respectively, 60% and 40% in the pronounced inflammation model. This is the first report showing that the endocytosis of nanoARC-Chol(ALN) by HUVECs magnifies the anti-inflammatory activity of ALN even under conditions of intense irritation

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