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

• conjugation to cysteine residues on antibodies or peptides, enabling site-specific and stable coupling [35]. PEG lipids modified with dibenzocyclooctyne (DBCO) or azide groups can undergo strain-promoted azide-alkyne cycloaddition. This click chemistry is advantageous when conjugating sensitive targeting

• moieties that might be adversely affected by harsh reaction conditions [36][37]. A selection of functionalized PEG lipids for ligand conjugation is shown in Figure 4. A study of engineered peptide-functionalized LNPs (pLNPs) used DSPE-PEG-maleimide as a linker to conjugate brain-targeting peptides

• including RVG29, T7, AP2, and mApoE through thiol-maleimide click chemistry [38][39][40]. The functionalized PEG lipid was incorporated by substituting 10%, 30%, or 50% of the total 1.5 mol % PEG lipid content with DSPE-PEG-maleimide in the LNP formulation. Peptides containing a terminal cysteine residue

Exploring the potential of polymers: advancements in oral nanocarrier technology

• Rousilândia de Araujo Silva,
• Igor Eduardo Silva Arruda,
• Luise Lopes Chaves,
• Mônica Felts de La Roca Soares and
• Jose Lamartine Soares Sobrinho

Beilstein J. Nanotechnol. 2025, 16, 1751–1793, doi:10.3762/bjnano.16.122

• invasiveness and greater biocompatibility [11]. Polymeric nanoparticles (PNs) have been studied for their potential in the oral delivery of insoluble drugs and biological products [12]. Peptides, such as GLP-1 receptor agonists [13], nucleic acids such as RNA [14], insulin [15], and antigens [16] have been

• , along with the mechanisms of active substance internalization and release within the body. Special attention is given to how PNs have been applied to enhance the oral delivery of peptides, nucleic acids, poorly soluble drugs, and small molecules. Additionally, current strategies for administration and

• , folic acid, peptides, and NPs smaller than 50 nm with surface charges between +15 and −15 mV are preferentially internalized via CvME. Some NPs follow clathrin- and caveolin-independent endocytosis pathways, which involve distinct uptake mechanisms, often dependent on cholesterol. These alternative

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

• penetration. Cell-penetrating peptides can improve aptamer transport by triggering adsorption-mediated endocytosis and may be an alternative strategy to solve this puzzle. For example, Le et al. [132] constructed nanocomplexes promising for the treatment of hepatocellular carcinoma by double modification of

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

Venom-loaded cationic-functionalized poly(lactic acid) nanoparticles for serum production against Tityus serrulatus scorpion

• Philippe de Castro Mesquita,
• Karla Samara Rocha Soares,
• Manoela Torres-Rêgo,
• Emanuell dos Santos-Silva,
• Mariana Farias Alves-Silva,
• Alianda Maira Cornélio,
• Matheus de Freitas Fernandes-Pedrosa and
• Arnóbio Antônio da Silva-Júnior

Beilstein J. Nanotechnol. 2025, 16, 1633–1643, doi:10.3762/bjnano.16.115

• polyethylenimine for loading peptides and proteins of T. serrulatus venom, and their use as a potential immunoadjuvant was evaluated. The protein loading efficiency of about 100% and the polyacrylamide gel electrophoresis assay confirmed the success of venom loading. Dynamic light scattering and zeta potential

• charged peptides, proteins, antigens, oligonucleotides, polypeptides, or DNA [18]. The PLA is well established to produce nanoparticles as carriers for drugs or biomolecules from a biotechnology source due to its natural metabolism pathway [25][26]. In a recent study, PLA was successfully employed to

• , peptides, DNA, RNA, antigens, and oligonucleotides to be efficiently incorporated through electrostatic interactions [35][36]. Moreover, some studies showed the interesting association of nanoparticles containing PEI for incorporation of DNA in gene transfection and BSA protein [14][37]. The

Cross-reactivities in conjugation reactions involving iron oxide nanoparticles

• Shoronia N. Cross,
• Katalin V. Korpany,
• Hanine Zakaria and
• Amy Szuchmacher Blum

Beilstein J. Nanotechnol. 2025, 16, 1504–1521, doi:10.3762/bjnano.16.106

• IONPs, using either amine- or carboxylic acid-functionalized IONPs, especially when biomolecules, such as proteins or peptides, are involved [3][7][8][9][10][11][12][13][14]. Sharpless et al. [6] have generally defined “click chemistry” as chemical processes that are highly selective, have a high

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

• therapeutic efficacy [118][128]. Additionally, liposomes can be surface-modified with various ligands such as antibodies, peptides, carbohydrates, and aptamers to achieve targeted drug delivery to specific cells or tissues [118][129]. These ligand-targeted liposomes can bind to receptors on target cells and

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

• tumor cell death by disrupting cholesterol signaling [72]. Therefore, HDL nanoparticles not only an effective drug carrier with inherent targeting ability but can also act as a therapeutic agent against cholesterol-dependent diseases. 1.3 Protein-based biomimetic nanoparticles Peptides and proteins are

• essential to maintain hemostasis by binding various biomolecules circulating in blood. They not only maintain the electrolyte and osmotic pressure but also deliver a variety of molecules across the body [73][74]. Peptides possess different functional groups on their surface that can act as a template for

• , a ligand of transferrin receptor, and NGR peptide, a ligand of CD13 [127]. Dual modification with the peptides yielded the ability to overcome the BBB and target the glioma. In another study, RBC-covered graphene oxide quantum dots (GTDC@M) were investigated regarding the targeted therapy of

Soft materials nanoarchitectonics: liquid crystals, polymers, gels, biomaterials, and others

• Katsuhiko Ariga

Beilstein J. Nanotechnol. 2025, 16, 1025–1067, doi:10.3762/bjnano.16.77

Polyurethane/silk fibroin-based electrospun membranes for wound healing and skin substitute applications

• Iqra Zainab,
• Zohra Naseem,
• Syeda Rubab Batool,
• Muhammad Waqas,
• Ahsan Nazir and
• Muhammad Anwaar Nazeer

Beilstein J. Nanotechnol. 2025, 16, 591–612, doi:10.3762/bjnano.16.46

• , and cytokines regulate the leucocytes at the injury site. Neutrophils (leucocytes) remove pathogens and necrotic tissues by phagocytosis, antimicrobial peptides, and the release of active oxygen species, proteolytic enzymes, as well as eicosanoids [39]. Excessive and uncontrolled inflammation causes

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

• aggregation of amyloid-β (Aβ) peptides, primarily Aβ40 and Aβ42. These oligomers typically consist of a limited number of Aβ monomers, often ranging from trimers to tetramers, but they can form larger aggregates under certain conditions. Their small size and unique structural properties contribute to several

• improved associated neurotoxicity [52]. Shifting from imaging to electrochemical approaches, researchers have developed biosensors comprising immobilized thiolated PrPC peptides on a graphene oxide/gold nanoparticle hydrogel electrode. This nanobiosensor displayed high specificity and sensitivity for

• therapeutic applications. CNMs can be categorized into three primary forms, namely, zero-dimensional fullerenes (e.g., C60), one-dimensional carbon nanotubes (CNTs), and two-dimensional graphene. Each of these NMs possesses distinct attributes that facilitate their engagement with proteins and peptides

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

• in ASO-based therapies. Some promising strategies to overcome these limitations involve the conjugation of ASOs with peptides [53], polymers [54], aptamers [55], and antibodies [56], as well as the development of novel drug delivery systems [57][58]. This review discusses the challenges associated

• synthetic approaches, that is, chemical–enzymatic synthesis (CES), solid-phase peptide synthesis (SPPS), and ring-opening polymerisation (ROP) of N-carboxy anhydrides [62]. While CES and SPPS offer access to structural isomers (i.e., α-PLL or ε-PLL) and sequence-controlled ʟ-lysine-rich peptides

• . These results underscored the potential of these nanocarriers as a non-invasive method for effective ASO delivery to the brain, offering a promising strategy for treating central nervous system disorders. Besides glycosylation, the utilisation of targeting sequenced peptides has also gained attention

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

• cellular functions. Future developments may see the integration of photothermal nanomaterial therapies with viruses, receptors, antibodies, aptamers, peptides, multifunctional genes, self-assembled DNA structures, and proteins. Given the diversity and adaptability of nanomaterials, it is conceivable to

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

• . Coating NCs with membranes from red blood cells or neutrophils or decorating them with peptides can camouflage the NCs and prevent macrophage ingestion [51][52]. 4.4 Endosomal escape After reaching the target site, as discussed in the previous paragraphs, NCs should release their cargo to exert their

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

• developed. Cell-penetrating peptides (CPPs), renowned for their ability to traverse biological membranes, have been extensively studied for their potential to enhance endosomal escape by causing membrane disruption [5]. However, the broad utility of CPPs is limited by their non-specific nature, which often

• endocytosis, likely due to membrane modulation by SO [18][19]. For AUR-Lipo (Figure 2c,f), amiloride significantly reduced fluorescence (p < 0.001), confirming that macropinocytosis is the primary pathway for AUR-Lipo. This is consistent with previous studies of cationic antimicrobial peptides using

• acid residues is crucial for the transmembrane insertion of peptides, particularly in acidic environments [21]. Our simulation data further indicate that, in the absence of protonation under these acidic conditions, there is no significant interaction between AUR and the membrane. This finding

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

• these carriers are improved [19][21][22][23][24][25]. Various cellular components such as extracellular vesicles, leukocyte and red blood cell membranes are beneficial for developing bioinspired devices. Specific targets, including peptides, aptamers, proteins, and viral capsids, may also be utilized in

• nanoparticles (AuNPs) with polyoxometalate and the peptides POMD and LPFFD (AuNPs@POMD-pep) have shown inhibition of Aβ1 aggregation and Aβ-induced cytotoxicity. However, the inherent toxicity of this formulation, challenges in particle digestion, and the potential for triggering immune reactions remain

Facile synthesis of size-tunable L-carnosine-capped silver nanoparticles and their role in metal ion sensing and catalytic degradation of p-nitrophenol

• Akash Kumar,
• Ridhima Chadha,
• Abhishek Das,
• Nandita Maiti and
• Rayavarapu Raja Gopal

Beilstein J. Nanotechnol. 2024, 15, 1576–1592, doi:10.3762/bjnano.15.124

• conductivity, and potent catalytic activity, make them ideal candidates for environmental monitoring and remediation [3]. Modifying silver nanoparticles with various biological molecules, peptides, proteins, and enzymes has further enhanced their functionality, stability, and selectivity towards specific

• pollutants [4][5][6]. Biomolecule-capped silver nanoparticles, particularly those stabilized by naturally occurring peptides such as ʟ-carnosine, have shown exceptional sensing and catalytic degradation capabilities. ʟ-Carnosine, a dipeptide consisting of β-alanine and histidine, stabilizes the nanoparticle

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

• hydrophilic drugs are entrapped in the lipid shell. PLHNPs demonstrate relatively greater loading capacity for lipophilic compounds than other nanoparticle systems [12][19]. Moreover, the surface modification of PLHNPs with targeting ligands, such as antibodies, peptides, or aptamers, has been explored to

• antibodies, peptides, aptamers, or small molecules that specifically bind to receptors overexpressed on the surface of target cells or tissues. The conjugation of targeting ligands to the surface of PLHNPs enables specific delivery of drug/phytochemicals to desired sites within the body, such as tumor cells

• 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

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

• administration also suffers from enzymatic degradation including peptidase and protease activity, making it challenging to deliver peptides and proteins [29][30]. Yet, the intranasal route still yields lower enzymatic degradation and higher bioavailability in the brain [31]. While the challenges of the

• critical literature reviews on N2B delivery of peptides and proteins. Considering the recent advancements and publications in the field, we highlight N2B delivery of biopharmaceuticals while emphasizing mAbs, RNA delivery, and NP functionalization techniques for better targeting the brain [150]. Despite

Dual-functionalized architecture enables stable and tumor cell-specific SiO₂NPs in complex biological fluids

• Iris Renata Sousa Ribeiro,
• Raquel Frenedoso da Silva,
• Romênia Ramos Domingues,
• Adriana Franco Paes Leme and
• Mateus Borba Cardoso

Beilstein J. Nanotechnol. 2024, 15, 1238–1252, doi:10.3762/bjnano.15.100

• performed with dithiothreitol and iodoacetamide, respectively, followed by in-gel trypsin digestion. The peptides were desalted on a C18 Stage Tips column and an aliquot containing 2 µg of each sample was analyzed using an LTQ Orbitrap Velos (Thermo Fisher Scientific) coupled to a nanoflow EASY-nLC (Proxeon

• Biosystems) liquid chromatography system through a Proxeon nanoelectrospray ion source. Peptides were separated at a flow rate of 300 nL/min in a 2–90% acetonitrile gradient in 0.1% formic acid for a total gradient time of 65 min (35% acetonitrile at 33 min) using a PicoFrit analytical column (20 cm × ID75

• ions. The 20 most intense peptide ions with charge state ≥2 were sequentially isolated to a target value of 5000 and fragmented by collision-induced dissociation in the linear ion trap using a normalized collision energy of 35%. Dynamic exclusion was enabled with an exclusion size list of 500 peptides

Realizing active targeting in cancer nanomedicine with ultrasmall nanoparticles

• André F. Lima,
• Giselle Z. Justo and
• Alioscka A. Sousa

Beilstein J. Nanotechnol. 2024, 15, 1208–1226, doi:10.3762/bjnano.15.98

• with targeting ligands (i.e., small molecules, peptides, or antibodies) that bind to overexpressed receptors within the tumor microenvironment. Despite the promise of nanomedicine, neither passive nor active delivery strategies have significantly improved clinical therapeutic outcomes for solid tumors

• through surface coating of the inorganic core with small molecules, such as glutathione (GSH), glucose, low molecular-weight polyethylene glycol (PEG), and various short peptides, among others [60][61][62][63]. This characteristic stands in sharp contrast to conventional large NPs, which often necessitate

• actively targeted usNPs can enhance tumor accumulation compared to non-targeted particles (Section 5). Furthermore, usNPs containing tumor homing and penetrating peptides can target the more accessible tumor vasculature, potentially aiding in particle accumulation within the tumor site [85][86]. A direct

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

• ] which can facilitate the transport of mRNA from endosomes and into the cytosol. There, it can be translated into peptides/proteins which can serve as antigens for the formation of antibodies against Covid-19 virus proteins. A key question regarding the possibility to benefit from using similar lipid

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

• oxide) (PEO). To improve the targeting ability of nanoparticles, ligands are typically designed to be located on the exterior of nanoparticles. Typically, ligands are cell-type-specific monoclonal antibodies, RGD peptides for the overexpression of the asialoglycoprotein receptor on cancer cells [5

Nanotechnological approaches in the treatment of schistosomiasis: an overview

• Lucas Carvalho,
• Michelle Sarcinelli and
• Beatriz Patrício

Beilstein J. Nanotechnol. 2024, 15, 13–25, doi:10.3762/bjnano.15.2

• sublethal doses can cause alterations in parasite tegument [85]. Bee venom comprises various pharmacologically active components, including melittin (constituting more than 50% of total proteins) and a mixture of enzymes, cell-lytic peptides, proteases, and bioactive amines [86]. This mixture has

Nanoarchitectonics of photothermal materials to enhance the sensitivity of lateral flow assays

• Elangovan Sarathkumar,
• Rajasekharan S. Anjana and
• Ramapurath S. Jayasree

Beilstein J. Nanotechnol. 2023, 14, 988–1003, doi:10.3762/bjnano.14.82

• and for efficient light-to-heat conversion. The surface chemistry of the selected photothermal material should facilitate the successful immobilization of biomolecules, such as antibodies, aptamers, peptides, or affinity molecules. Finally, an efficient thermal energy readout system is needed for the