PEGylated lipids in lipid nanoparticle delivery dynamics and therapeutic innovation

• Peiyang Gao

Beilstein J. Nanotechnol. 2025, 16, 1914–1930, doi:10.3762/bjnano.16.133

• address PEGylation associated immunogenicity. By conducting a critical analysis of the recent literature and identifying potent candidates for PEGylation strategies or PEG-free platforms, this review aims to provide insights and support the advancement of LNP mediated delivery. Keywords: functionalized

• PEG; immunogenicity; lipid nanoparticles; PEG alternatives; PEG lipids; therapeutic delivery; Review Introduction Lipid nanoparticles (LNPs) have become a promising platform in modern nanomedicine, especially for delivering genetic payloads such as mRNA and siRNA. These nanoscale particles can

• strategies in LNP-based drug delivery systems, approaches are being explored. These include integrating functional groups into PEG lipids for ligand conjugation and improved cell-specific targeting, as well as developing PEG alternatives to mitigate anti-PEG antibody associated immunogenicity [7][8]. This

Advances of aptamers in esophageal cancer diagnosis, treatment and drug delivery

• Yang Fei,
• Hui Xu,
• Chunwei Zhang,
• Jingjing Wang and
• Yong Jin

Beilstein J. Nanotechnol. 2025, 16, 1734–1750, doi:10.3762/bjnano.16.121

• aptamers in terms of global market share. However, the large size of antibodies (150–180 kDa, 15 nm), limited tissue permeability, expensive, time-consuming and laborious in vivo screening, and high immunogenicity [26] make it imperative to develop safe, effective, and simple ApDCs. Aptamer-functionalized

Prospects of nanotechnology and natural products for cancer and immunotherapy

• Jan Filipe Andrade Santos,
• Marcela Bernardes Brasileiro,
• Pamela Danielle Cavalcante Barreto,
• Ligiane Aranha Rocha and
• José Adão Carvalho Nascimento Júnior

Beilstein J. Nanotechnol. 2025, 16, 1644–1667, doi:10.3762/bjnano.16.116

• biological environments, potential immunogenicity, scalability of manufacturing processes, and the need for comprehensive long-term toxicity studies [20][21]. Overcoming biological barriers, such as penetration through the dense tumor extracellular matrix, also remains a major hurdle [19]. Nevertheless

• benefits of this technology are reduced toxicity and immunogenicity, as well as less complexity, since they do not implement synthetic carriers in their composition. However, carrier-free self-assembly nanoparticles may have some limitations, such as the limitation of natural products used, since the

Ferroptosis induction by engineered liposomes for enhanced tumor therapy

• Alireza Ghasempour,
• Mohammad Amin Tokallou,
• Mohammad Reza Naderi Allaf,
• Mohsen Moradi,
• Hamideh Dehghan,
• Mahsa Sedighi,
• Mohammad-Ali Shahbazi and
• Fahimeh Lavi Arab

Beilstein J. Nanotechnol. 2025, 16, 1325–1349, doi:10.3762/bjnano.16.97

• ferroptosis-based therapy. Among them, engineered liposomes have received more attention due to their biocompatibility, low immunogenicity, and flexibility in chemical and structural modifications. The present review focuses on the mechanisms of ferroptosis and its induction by engineered liposomes to improve

• liposomes hold promise for drug delivery and ferroptosis induction, but their potential toxicity and immunogenicity require careful consideration. Although the phospholipid bilayer of liposomes has the advantage of resembling cells, one of the main causes of chemical instability is the possibility of

• designed to reduce systemic toxicity, some formulations, particularly cationic liposomes, can be cytotoxic to macrophages and disrupt immunomodulatory signaling. Liposomal immunogenicity depends on factors like surface charge, size, and PEGylation, with positively charged liposomes often triggering

Better together: biomimetic nanomedicines for high performance tumor therapy

• Imran Shair Mohammad,
• Gizem Kursunluoglu,
• Anup Kumar Patel,
• Hafiz Muhammad Ishaq,
• Cansu Umran Tunc,
• Dilek Kanarya,
• Mubashar Rehman,
• Omer Aydin and
• Yin Lifang

Beilstein J. Nanotechnol. 2025, 16, 1246–1276, doi:10.3762/bjnano.16.92

• inherent traits endow biomimetic nanoparticles with a suite of intelligent features, including biocompatibility, low immunogenicity, reduced toxicity, immune evasion, prolonged circulation, homotypic binding, enhanced tumor targeting, and the capability of precise delivery. By integrating biologically

• vaccines and improving their immunogenicity [112]. The presence of viral nucleic acids has been a key concern in medical applications, which limits the use of viruses in living organisms. Virus-like particles are multimeric nanoparticles consisting of viral proteins but lack viral genetic material. Thus

A calix[4]arene-based supramolecular nanoassembly targeting cancer cells and triggering the release of nitric oxide with green light

• Cristina Parisi,
• Loredana Ferreri,
• Tassia J. Martins,
• Francesca Laneri,
• Samantha Sollima,
• Antonina Azzolina,
• Antonella Cusimano,
• Nicola D’Antona,
• Grazia M. L. Consoli and
• Salvatore Sortino

Beilstein J. Nanotechnol. 2025, 16, 1003–1013, doi:10.3762/bjnano.16.75

• immunogenicity and paving the way for a variety of applications in the biomedical field [1][6][7][8][9]. Due to their amphiphilic character, calix[n]arene derivatives can self-assemble in water medium, leading to nanoaggregates exhibiting much better hosting performances than the single monomers [10]. Aggregates

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

• NPs led to a higher permeability of RA and CUR across the BBB. This suggests that the antibody plays a crucial role in improving the uptake of NPs by cells and drug delivery to the brain [65]. Additionally, antibody conjugation can help to reduce the immunogenicity of NPs, enhancing their safety and

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

• past decade demonstrating how these polymers improve gene silencing efficiencies, particularly in cancer and neurodegenerative disease models. Despite the progress achieved, barriers such as immunogenicity, delivery limitations, and scalability still need to be overcome for broader clinical application

• further be reduced through PEGylation, which offers significant advantages by addressing common limitations of dendrimer-based systems such as drug leakage, immunogenicity, and poor ASO solubility [144]. Patil et al. demonstrated that PAMAM-b-PEG3000-b-PLL–siRNA triblock copolymers exhibited reduced

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

• (i.e., oxidation) of their surface, CNs with optimal hydrophobic/hydrophilic properties and increased dispersibility can be obtained as preconditions for biocompatibility and low immunogenicity. Also, improved electronic, mechanical, and thermal properties as preconditions for (photo)thermal and

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

• , consequently, sustained and controlled release of potential associated drugs [21]. To overcome these limitations and enhance coating efficiency, the decoration of nanostructures with functional ligands increases their biological interactions. Decreasing nonspecific interactions and immunogenicity is one of the

Liver-targeting iron oxide nanoparticles and their complexes with plant extracts for biocompatibility

• Shushanik A. Kazaryan,
• Seda A. Oganian,
• Gayane S. Vardanyan,
• Anatolie S. Sidorenko and
• Ashkhen A. Hovhannisyan

Beilstein J. Nanotechnol. 2024, 15, 1593–1602, doi:10.3762/bjnano.15.125

• adverse reactions. The toxicity of MNPs depends on various factors such as size, shape, structure, surface modification, concentration, dosage, biodistribution, bioavailability, solubility, immunogenicity, and pharmacokinetics [23][24]. Their use in some clinical applications is limited by low solubility

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

• . This leads to improved bioavailability and allows for sustained release of the encapsulated therapeutic agents [64][65][66]. The advantages of PEGylated PLHNPs include enhanced biocompatibility and reduced immunogenicity. The PEG layer creates a hydrophilic barrier around the nanoparticles, which

Radiofrequency enhances drug release from responsive nanoflowers for hepatocellular carcinoma therapy

• Yanyan Wen,
• Ningning Song,
• Yueyou Peng,
• Weiwei Wu,
• Qixiong Lin,
• Minjie Cui,
• Rongrong Li,
• Qiufeng Yu,
• Sixue Wu,
• Yongkang Liang,
• Wei Tian and
• Yanfeng Meng

Beilstein J. Nanotechnol. 2024, 15, 569–579, doi:10.3762/bjnano.15.49

• immunogenicity, and their application is limited by high costs [6]. In addition to the aforementioned treatments, systemic chemotherapy drugs including sorafenib and lenvatinib have been shown to be effective at improving overall survival. Nonetheless, patients often discontinue these treatments due to

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

• microenvironment. Guo et al. used the major histocompatibility complex class I (MHC I)-deficient 4T1 breast cancer cell membrane to coat dexamethasone (DXM)-loaded biomimetic NPs, endowing them with lower immunogenicity, thus, preventing stimulation of the immune system [22]. The NPs enabled the targeted delivery

Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

• Filip Gorachinov,
• Fatima Mraiche,
• Diala Alhaj Moustafa,
• Ola Hishari,
• Yomna Ismail,
• Jensa Joseph,
• Maja Simonoska Crcarevska,
• Marija Glavas Dodov,
• Nikola Geskovski and
• Katerina Goracinova

Beilstein J. Nanotechnol. 2023, 14, 240–261, doi:10.3762/bjnano.14.23

• such as cyclodextrin, inulin, and chitosan. These polymers are used alone or combined with amphiphilic polymers for core–shell nanoparticles such as the triblock polymer poly(ʟ-lactide)-poly(ethylene glycol)-poly(ʟ-lactide) (PLLA-PEG-PLLA) to increase the stability and decrease the immunogenicity of

• relationships of the LNPs are discovered by building and evaluating different LNP libraries [153]. Studies should also intensify in the area of nanoscale biointerface interactions and their influence on specific targeting and internalization, improved tolerability, and the reduction of immunogenicity and off

Bioselectivity of silk protein-based materials and their bio-inspired applications

• Hendrik Bargel,
• Vanessa T. Trossmann,
• Christoph Sommer and
• Thomas Scheibel

Beilstein J. Nanotechnol. 2022, 13, 902–921, doi:10.3762/bjnano.13.81

• , slow biodegradation, low immunogenicity, and non-toxicity, making them ideally suited for tissue engineering and biomedical applications. Furthermore, recombinant production technologies allow for application-specific modification to develop adjustable, bioactive materials. The present review focusses

• by extraordinary properties including excellent biocompatibility, slow biodegradation, low immunogenicity, and non-toxicity, making them ideally suited for tissue engineering and biomedical applications [105][106][107]. This review focuses on achievements made with silk-based protein materials and

• care, shampoos, and lotions. Traditional utilization of silk fibres as sutures for wounds are known for centuries due to their strength, biocompatibility, and low immunogenicity [104], and silkworm silk surgical threads are commercially available [108]. Moreover, silk-based polymeric materials have

Recent advances in nanoarchitectures of monocrystalline coordination polymers through confined assembly

• Lingling Xia,
• Qinyue Wang and
• Ming Hu

Beilstein J. Nanotechnol. 2022, 13, 763–777, doi:10.3762/bjnano.13.67

• assembled vaccine particles showed improved immunogenicity. Moreover, the activity of the encapsulated OVA and CpG was maintained under enzyme incubation, heating treatment (60 °C for 12 h), or long-term storage (longer than six months) at 25 °C. The efficiency of this strategy encourages large-scale

Design and selection of peptides to block the SARS-CoV-2 receptor binding domain by molecular docking

• Kendra Ramirez-Acosta,
• Ivan A. Rosales-Fuerte,
• J. Eduardo Perez-Sanchez,
• Alfredo Nuñez-Rivera,
• Josue Juarez and
• Ruben D. Cadena-Nava

Beilstein J. Nanotechnol. 2022, 13, 699–711, doi:10.3762/bjnano.13.62

• (K417N, Y453F, E484K, and N501Y), according to the B1.1.7, B.1.351, P.1, and Y453F SARS-CoV-2 variants. Computing the radius of gyration The radius of gyration (Rg) for the selected peptides against SARS-CoV-2 was determined using the WinHydroPro V10 software [35]. Immunogenicity analysis Immunogenicity

• were increased. These results support the success of the chosen strategy for designing peptides based on the hydrogen bond interactions in an easy way. Immunogenicity The immune system can recognize external molecules introduced into our body, which, in many cases, leads to the production of antibodies

• , nucleic acids, and even drugs) do not reach their target since they are eliminated by cells of the immune system, which limits their activity. Therefore, proposed peptides with antiviral activity must be evaluated from the immunological point of view. In this context, an immunogenicity prediction of the

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 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

Wet-spinning of magneto-responsive helical chitosan microfibers

• Dorothea Brüggemann,
• Johanna Michel,
• Naiana Suter,
• Matheus Grande de Aguiar and
• Michael Maas

Beilstein J. Nanotechnol. 2020, 11, 991–999, doi:10.3762/bjnano.11.83

• immunogenicity [17] and, therefore, has become highly used in tissue regeneration [18][19]. Chitosan fibers are particularly well-suited for tissue engineering due to their highly porous scaffold architecture [20]. Using electrospinning, chitosan fibers can be produced with a diameter ranging from several tens

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

• interesting properties. They can be easily synthetized and coated or conjugated to carry various cargos, from small molecules to proteins and nucleic acids [174]. Furthermore, AuNPs show low immunogenicity and toxicity due to their inert core [78]. Finally, AuNPs could be used as X-ray contrast agent if their

Preparation and in vivo evaluation of glyco-gold nanoparticles carrying synthetic mycobacterial hexaarabinofuranoside

• Gennady L. Burygin,
• Polina I. Abronina,
• Nikita M. Podvalnyy,
• Sergey A. Staroverov,
• Leonid O. Kononov and
• Lev A. Dykman

Beilstein J. Nanotechnol. 2020, 11, 480–493, doi:10.3762/bjnano.11.39

• shown to influence the immunogenicity of conjugates with haptens. Large spherical GNPs (d = 15 and 50 nm) are the optimal antigen carriers and adjuvants for immunization [96]. Nature and length of the spacers (linkers) have been selected to modulate the stability of the Ara6-GNPs, as well as to control

• the presentation of the Ara6 hexasaccharide epitope on the surface of the GNPs in order to explore the effect of a linker on the immunogenicity. The very short C2 linker (only two aliphatic carbon atoms) of glycoside 1 was chosen to allow the Ara6 hexasaccharide moiety to protrude just a little above

• noted above; see also the subsequent discussion on the putative mechanism of immunogenicity of glyco-GNPs). This also suggests that the increased stability of glyco-GNPs does not necessarily mean better immunization. Although one can argue that amine-linked carbohydrate ligands present in Ara6-GNPs 3

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

• degree of biocompatibility make plant viruses capsids suitable candidates as carriers to deliver therapeutic drugs or siRNA molecules. Immunogenicity of CCMV and BMV The RAW 264.7-blue macrophage cell line was used to determine the potential immune response in vitro of both BMV and CCMV viruses

• been reported using papaya mosaic virus [45]. Both capsids of CCMV and BMV were covered with polyethylene glycol (PEG) to decrease their surface charge and mask the domains of the capsid proteins that could be recognized by the macrophages (Figure 3C,D). PEG is widely used to reduce the immunogenicity

• protein immunogenicity [46]. Although the PEGylation of CCMV capsids (CCMV-PEG) greatly reduced the immunogenic response, BMV seems to be a better nanocarrier candidate due to its low immunological response. On the other hand, and despite of the immunogenicity of CCMV, which can limit its use for certain

Poly(1-vinylimidazole) polyplexes as novel therapeutic gene carriers for lung cancer therapy

• Gayathri Kandasamy,
• Elena N. Danilovtseva,
• Vadim V. Annenkov and
• Uma Maheswari Krishnan

Beilstein J. Nanotechnol. 2020, 11, 354–369, doi:10.3762/bjnano.11.26

• context, non-viral vectors have garnered interest in recent years as gene delivery vehicles. But the highly cationic nature of the employed carriers is associated with immunogenicity and toxicity. Further, the ability of these carriers to escape the acidic endosomes in the cells limit their transfection