Nanomaterials in targeting amyloid-β oligomers: current advances and future directions for Alzheimer's disease diagnosis and therapy

• Shiwani Randhawa,
• Trilok Chand Saini,
• Manik Bathla,
• Rahul Bhardwaj,
• Rubina Dhiman and
• Amitabha Acharya

Beilstein J. Nanotechnol. 2025, 16, 561–580, doi:10.3762/bjnano.16.44

• early detection and the identification of reliable biomarkers and therapeutic targets. Moreover, the blood–brain barrier (BBB) poses a significant obstacle to effective drug delivery, further hindering the development of successful treatments. Nanomaterials (NMs) offer promising solutions for the early

Synthetic-polymer-assisted antisense oligonucleotide delivery: targeted approaches for precision disease treatment

• Ana Cubillo Alvarez,
• Dylan Maguire and
• Ruairí P. Brannigan

Beilstein J. Nanotechnol. 2025, 16, 435–463, doi:10.3762/bjnano.16.34

• study, Min et al. investigated the use of PLL to develop glucose-coated polymeric nanocarriers for the systemic delivery of ASOs across the blood–brain barrier (BBB) [71]. The authors utilised a polyion complex micelle (PIC/M) platform based on poly(ethylene glycol)-b-poly(ʟ-lysine) (PEG–PLL, DPPLL = 42

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

• for active agent loading and functionalization with (intra)cellular component targeting ligands, and extremely small size for crossing the blood–brain barrier (BBB) and targeted delivery to the brain. The hydrophobic nature of the CNs offers good membrane permeability. Through chemical modifications

Recent advances in photothermal nanomaterials for ophthalmic applications

• Jiayuan Zhuang,
• Linhui Jia,
• Chenghao Li,
• Rui Yang,
• Jiapeng Wang,
• Wen-an Wang,
• Heng Zhou and
• Xiangxia Luo

Beilstein J. Nanotechnol. 2025, 16, 195–215, doi:10.3762/bjnano.16.16

• adjacent healthy cells [109]. After eliminating tumor cells, small gold nanorods can penetrate the blood–brain barrier and be effectively excreted from the body through renal excretion, thereby avoiding the production of VNBs near non-cancerous cells. 3.2 Posterior capsule opacity after cataract surgery

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

• . Intranasal delivery has emerged as a promising strategy for targeting the central nervous system by bypassing the blood–brain barrier (BBB). This approach was demonstrated by the nose-to-brain administration of D6-cholestrol-loaded liposomes, which led to an accumulation of D6-cholesterol in the brain in

Biomimetic nanocarriers: integrating natural functions for advanced therapeutic applications

• Hugo Felix Perini,
• Beatriz Sodré Matos,
• Carlo José Freire de Oliveira and
• Marcos Vinicius da Silva

Beilstein J. Nanotechnol. 2024, 15, 1619–1626, doi:10.3762/bjnano.15.127

• employed in treating other diseases, such as Alzheimer's disease. Current medications for Alzheimer's face the challenge of the blood–brain barrier (BBB), which includes the blood–brain, cerebrospinal fluid–brain, and blood–cerebrospinal fluid barriers. These barriers exhibit high selectivity in drug

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

• therapeutic effects [30][31]. Poor permeability and penetration are additional obstacles. Phytochemicals may have difficulties crossing biological membranes, such as the intestinal epithelium or the blood–brain barrier, because of their molecular size, polarity, or lipophilicity. Poor permeability limits the

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

• /bjnano.15.113 Abstract Central nervous system diseases negatively affect patients and society. Providing successful noninvasive treatments for these diseases is challenging because of the presence of the blood–brain barrier. While protecting the brain’s homeostasis, the barrier limits the passage of

• small or large molecules from the current literature, we highlight the preclinical studies and their results to prove the strategies’ success and limitations. Keywords: antibody delivery; biopharmaceutical delivery; blood–brain barrier (BBB); CNS diseases; drug delivery; hybrid nanoparticles

• considered a challenge because of the existence of the blood–brain barrier (BBB, Figure 1), which is composed of several cell types [7]. The BBB is a dynamic and selective interface between the systemic circulation and the brain [8]. The structure of the healthy BBB relies on the endothelial cells and the

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

• delivery methods that can effectively cross the blood–brain barrier are essential for delivering therapeutic agents to the brain [40]. Nanotechnology has emerged as a promising tool in smart delivery systems. Nanoparticles can be designed to pass through biological barriers and reach specific sites in the

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

• of cells with drugs may allow drug incorporation into vesicles released by the cells. Recent studies have even suggested that incorporation of drug-containing NPs in cellular membranes might increase the ability of these particles to cross the blood–brain barrier [6]. However, regulatory challenges

On the additive artificial intelligence-based discovery of nanoparticle neurodegenerative disease drug delivery systems

• Shan He,
• Julen Segura Abarrategi,
• Harbil Bediaga,
• Sonia Arrasate and
• Humberto González-Díaz

Beilstein J. Nanotechnol. 2024, 15, 535–555, doi:10.3762/bjnano.15.47

• diseases are characterized by slowly progressing neuronal cell death. Conventional drug treatment strategies often fail because of poor solubility, low bioavailability, and the inability of the drugs to effectively cross the blood–brain barrier. Therefore, the development of new neurodegenerative disease

• inadequate solubility, limited bioavailability, and inability to effectively penetrate the blood–brain barrier (BBB) [6]. Therefore, there is an urgent need to focus on the advancement of novel neurodegenerative disease drugs (NDDs) [7][8]. The major obstacle encountered by NDDs is the selectivity of the BBB

Classification and application of metal-based nanoantioxidants in medicine and healthcare

• Nguyen Nhat Nam,
• Nguyen Khoi Song Tran,
• Tan Tai Nguyen,
• Nguyen Ngoc Trai,
• Nguyen Phuong Thuy,
• Hoang Dang Khoa Do,
• Nhu Hoa Thi Tran and
• Kieu The Loan Trinh

Beilstein J. Nanotechnol. 2024, 15, 396–415, doi:10.3762/bjnano.15.36

• because most drugs cannot cross the blood–brain barrier (BBB) [115][116]. Besides, the accumulation of drugs at damaged areas of the BBB can lead to an unprotected, disrupted BBB and to disturbances of the brain microenvironment. In contrast, the integrity of the BBB can decrease the accumulation of drugs

• other medicines, which significantly limits their applications in clinical practice. Some common barriers include blood–brain barrier, gastrointestinal barrier, cellular membrane, and blood vessel fenestration [195]. Although scientists have made significant effort in solving this problem, only a few

Elasticity, an often-overseen parameter in the development of nanoscale drug delivery systems

• Agnes-Valencia Weiss and
• Marc Schneider

Beilstein J. Nanotechnol. 2023, 14, 1149–1156, doi:10.3762/bjnano.14.95

• barriers besides cellular membranes need to be addressed. A few examples of these barriers are penetration in or permeation through mucus, skin penetration, overcoming the blood brain barrier, or extravasation from blood vessels. Another challenge is the accumulation of particulate drug delivery systems in

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

• 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

Quercetin- and caffeic acid-functionalized chitosan-capped colloidal silver nanoparticles: one-pot synthesis, characterization, and anticancer and antibacterial activities

• Akif Hakan Kurt,
• Elif Berna Olutas,
• Fatma Avcioglu,
• Hamza Karakuş,
• Mehmet Ali Sungur,
• Cansu Kara Oztabag and
• Muhammet Yıldırım

Beilstein J. Nanotechnol. 2023, 14, 362–376, doi:10.3762/bjnano.14.31

• conventional treatments. This resistance is mostly due to the blood–brain barrier, which is the most important obstacle to drug distribution. Since nanoparticles can penetrate through the blood–brain barrier, they are a preferred medicine in brain and nervous system diseases. In glioblastoma multiforme

Polymer nanoparticles from low-energy nanoemulsions for biomedical applications

• Santiago Grijalvo and
• Carlos Rodriguez-Abreu

Beilstein J. Nanotechnol. 2023, 14, 339–350, doi:10.3762/bjnano.14.29

• showed that the PLGA nanoparticles functionalized with 8D3 antibody were able to cross the blood–brain barrier (BBB) as demonstrated by the analgesic effect of encapsulated loperamide on mice. PLGA nanoparticles prepared using Polysorbate 80 with the same formulation discussed above (diameter ca. 27 nm

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

• (CNS), where endothelial cells form the tightest and the most selective blood–brain barrier (BBB) that provides protection against the penetration of harmful substances and pathogens. Other types of connections include adherens junctions, maintained primarily by transmembrane VE-cadherin, and gap

Recent progress in cancer cell membrane-based nanoparticles for biomedical applications

• Qixiong Lin,
• Yueyou Peng,
• Yanyan Wen,
• Xiaoqiong Li,
• Donglian Du,
• Weibin Dai,
• Wei Tian and
• Yanfeng Meng

Beilstein J. Nanotechnol. 2023, 14, 262–279, doi:10.3762/bjnano.14.24

• cells have also been found to have the ability to penetrate the blood‒brain barrier (BBB) in some special cases [26][27]. As a highly specialized structure, the BBB maintains homeostasis of the central nervous system [48]. The targeted delivery of drugs to the brain is challenging because of the limited

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

• small size of nanomaterials enables them to permeate through biological barriers in the body, such as the blood–brain barrier, the pulmonary system, and through the tight junction of endothelial cells of the skin. The main goal of loading drugs on nanomaterials is the delivery to specific target cells

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

• , which yielded a dual targeting structure that was able to cross the blood–brain barrier, a significant obstacle when treating brain tumors. Similarly, an improved internalization of CUR-loaded MNP was also observed in HPAF-II and Panc-1 human pancreatic cancer cell lines (54.06% and 53.86%, respectively

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

Transient coating of γ-Fe₂O₃ nanoparticles with glutamate for its delivery to and removal from brain nerve terminals

• Konstantin Paliienko,
• Artem Pastukhov,
• Michal Babič,
• Daniel Horák,
• Olga Vasylchenko and
• Tatiana Borisova

Beilstein J. Nanotechnol. 2020, 11, 1381–1393, doi:10.3762/bjnano.11.122

• glutamate homeostasis and synaptic neurotransmission. Also, glutamate plays an important role in mediating the blood–brain barrier function and can be exploited for clinical translation [38]. It was shown that the conjugation of non-permeable drugs with glutamate may improve the brain delivery of the drug

• [39]. The neuronal release of glutamate modulates the blood–brain barrier function, through activation of N-methyl-ᴅ-aspartate (NMDA) receptors [40]. Glutamate increased intracellular calcium levels in endothelial cells and levels of nitrogen oxide (NO) around microvessels. These results can be

• considered in support of a mechanism of glutamate-induced activation of NMDA receptors in endothelial cells, which leads to calcium signaling and downstream NO production to promote blood–brain barrier permeability [38]. Thus, it may be expected that glutamate-conjugated γ-Fe2O3 nanoparticles can more easily

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

• inefficient methodology of use, and inconsistent results [94]. The potential toxicity could be put to a good use, though. Hybrid Fe3O4/Gd2O3 loaded with cisplatin and tagged with lactoferrin and RGD (a cell endocytosis small peptide) was proved in vitro and in vivo to cross the blood–brain barrier and target

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

• Central nervous system diseases are a heavy burden on society and health care systems. Hence, the delivery of drugs to the brain has gained more and more interest. The brain is protected by the blood–brain barrier (BBB), a selective barrier formed by the endothelial cells of the cerebral microvessels

• nanoparticles (AuNPs); blood–brain barrier (BBB); drug delivery; liposomes; nanomedicine; polymeric nanoparticles; solid lipid nanoparticles; superparamagnetic iron oxide nanoparticles (SPIONs); Introduction Neurological disorders and brain diseases are real burdens for modern societies and healthcare systems

• damaged by ischemia [2]. One of the main limitations for the treatment of neurological disorders is the difficulty to deliver drugs to the brain. The brain is surrounded by the blood–brain barrier (BBB), a selective barrier formed by the endothelial cells of the cerebral microvessels [3][4]. The surface

Frontiers in pharmaceutical nanotechnology

• Matthias G. Wacker

Beilstein J. Nanotechnol. 2019, 10, 2538–2540, doi:10.3762/bjnano.10.244

• science. They have fundamentally changed our understanding of the way dosage forms can facilitate drug therapy. Prof. Jörg Kreuter has been a pioneer in this research area and dedicated his life’s work to nanoparticle research and the blood–brain barrier [2]. One of his most outstanding discoveries, the