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

• 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

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

• Figure 1. To address this challenge, and given that cysteine promotes both mucoadhesion and the opening of tight junctions, Han et al. [117] developed a trimethyl chitosan–cysteine conjugate (GTC) to formulate PNs for the co-delivery of antitumor shRNA and siRNA via oral administration. These therapeutic

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

• -delivery of a P-glycoprotein (P-gp) inhibitor, specifically, small interfering RNA (siRNA) against the MDR1 gene, along with the chemotherapeutic agent doxorubicin (DOX). This system capitalizes on the high-affinity binding of the AS1411 aptamer to nucleolin, a protein overexpressed on the surface of

• cancer cells, thereby significantly enhancing tumor-specific drug accumulation. Concurrently, siRNA-mediated silencing of MDR1 effectively suppresses P-gp-mediated drug efflux, overcoming multidrug resistance (MDR) in tumor cells. By integrating active targeting, gene silencing, and chemosensitization

• , coupling drugs, covalent binding with siRNA, and chemical modification [34][35] to promote their role in cancer drug delivery. Conventional drug delivery systems, including metal nanoparticles, nanohydrogels, liposomes, and polymeric micelles [36][37][38], have gained widespread adoption due to their

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

• achieve high accumulation at the disease site with maximum internalization and endosomal escape [144]. In a recent study, Walweel et al. engineered a novel cationic star copolymer to deliver LC3 siRNA efficiently into TNBC cells. The polycationic structure provided strong electrostatic condensation with

• siRNA and enabled proton sponge-mediated endosomal escape, ensuring cytoplasmic release of the gene cargo. These LC3siRNA-loaded nanoparticles (LC3siRNA-NPs) exhibited pH-responsive behavior, enhanced cellular uptake, and potent suppression of autophagy. In vitro and in vivo experiments demonstrated

• structural parameters including charge, shape, and size [146]. Importantly, various problems exist associated with exogenous siRNA/genes, including easy degradation, short circulation time, immune clearance, low accumulation, and inability to penetrate the target cell membrane [147][148]. Gene therapy paves

Serum heat inactivation diminishes ApoE-mediated uptake of D-Lin-MC3-DMA lipid nanoparticles

• Demian van Straten,
• Luuk van de Schepop,
• Rowan Frunt,
• Pieter Vader and
• Raymond M. Schiffelers

Beilstein J. Nanotechnol. 2025, 16, 740–748, doi:10.3762/bjnano.16.57

• ) ionizable lipids. Cellular uptake and siRNA delivery efficiency of the LNPs were determined in media containing untreated or heat-inactivated serum. Mechanistically, we found that apolipoprotein E, a protein corona component that is crucial for MC3 LNP tropism, displayed reduced stability and functionality

• intravenously after which they are dependent on the adsorption of the plasma protein apolipoprotein E (ApoE) to their surface to efficiently target LDL-receptor expressing cells in the liver and deliver the siRNA cargo [25][26]. As the protein corona seems to play a pivotal role in LNP tissue distribution and

• (2000)-biotin) were obtained from Avanti. Human recombinant ApoE3 was purchased from Fitzgerald Industries. Mouse monoclonal anti-ApoE (NB110-60531; Bio-Techne), FITC labelled goat anti-mouse secondary antibody (A28175; ThermoFischer). Anti-firefly siRNA molecules were ordered as individual strands at

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

• oligomer (PMO); phosphorothioate (PS); polyplexes; ribose substitutions; small interfering RNA (siRNA); synthetic polymers; tricyclo-DNA (tcDNA); Introduction The development and use of personalised therapies tailored to individual patients have emerged as a powerful strategy for treating various

• cellular internalisation [14]. Antisense oligonucleotides (ASOs) are short, chemically engineered single- or double-stranded oligonucleotides (also known as small interfering RNA, siRNA) that bind to complementary RNA in a sequence-specific manner, causing the suppression, modification, or restoration of a

• branched PEGylated poly-ʟ-ornithine (PEG-PLO) to form a unit polyion complex (uPIC) with PRDM14-specific chimeric siRNA, which was administered intravenously to mouse models. PEG-PLO exhibited longer retention times in the bloodstream and enhanced accumulation in tumour tissues, leading to a significant

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

• stimulated the activation of T-cells and natural killer cells, resulting in significant tumor regression [72]. Small interfering RNA (siRNA) therapeutics: siRNAs are double-stranded RNA molecules that induce the degradation of specific mRNAs, effectively silencing their expression. This approach has shown

• promise in mitigating inflammation and promoting tumoricidal macrophage polarization. For inflammatory diseases like IBD, targeting pro-inflammatory cytokines with siRNA has proven effective. Laroui et al. developed polymeric NPs made of poly(lactic acid)–poly(ethylene glycol) block copolymer (PLA-PEG

• ) grafted with the Fab’ fragment of F4/80 antibodies for specific macrophage targeting. These Fab’-bearing NPs delivered TNF-α siRNA to the colonic macrophages of mice, attenuating colitis more efficiently than non-targeted systems [73]. In cancer therapy, siRNAs have been used to reprogram TAMs to the M1

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

• progress in clinical trials [141][142] although only a limited amount of the CD20 antibodies can cross the BBB. This can be attributed to their large size and degradation-prone nature [143][144]. In addition, therapy with small interfering RNA (siRNA) is also considered a powerful tool for modulating gene

• expression through gene silencing, and it can open new doors for disease treatments [145]. Currently, patisiran, givosiran, lumasiran, inclisiran, nedosiran, and vutrisiran are siRNA-based drugs approved by FDA for treating different diseases [146]. Besides these successful efforts, their delivery to the

• were treated with the NPs, the median survival was increased by a factor of 1.37 [155]. Regarding RNA delivery, recent literature specifically stresses the delivery of siRNA. siRNAs are regarded as an effective and attractive strategy to inhibit specific genes; therefore, there is the possibility of

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

• peptide-based micelle nanocomplex for delivering Pcbp2 siRNA as gene-silencing agent [74]. The surface of the nanocarrier was modified with a dimeric IGF2R peptide as a M6PR-targeting ligand of the activated HSCs. The use of cholesteryl peptide to construct the nanocarrier facilitated in vitro cellular

• , siCol1α1 and siTIMP-1 siRNAs were used to inhibit collagen synthesis and to promote collagen degradation, respectively. The spherical lipid NPs with a mean particle size of 140 ± 0.12 nm and negative zeta potential (−12.9 mV) were constructed from amphiphilic cationic hyperbranched lipoids for siRNA

• cellular uptake results accordingly affected the in vitro gene silencing activity as shown in decreased expression of Col1α1 and TIMP-1 after administering the nanocarriers. The in vivo cellular localization of siRNA-VLNPs in the liver tissue was evaluated in CCl4-treated mice. The result shows that 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

• have outlined some of the common endocytic pathways in cells. Although we can currently manipulate molecules involved in various pathways in a specific way by siRNA, gene knockout, or CRISPR/Cas, the induced changes can have secondary effects that are not easy to predict. Also, overexpression of

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

• their high potential applications in various fields, including theragnostics. The PLGA SPION nanoparticles were modified to carry siRNA for silencing the inflammatory cytokine Cox-2 in activated macrophages and to serve as a tracer for locating activated macrophages in a mouse model of intra-uterine

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

• based on specific issues. In addition, we considered only plasmid-based transfection systems during literature search (see details about experimental approach and scope in Supporting Information File 1). But we would expect a similar outcome and trend for the mRNA or siRNA NP delivery literature. The

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

• tumor tissue, such as mRNA, siRNA, miRNA, and sgRNA [113]. This strategy can avoid the impact on normal tissues and shows the advantage of low cytotoxicity. However, RNA is highly unstable and can be easily degraded and eliminated by the kidney [114]. Gene delivery technology based on biomimetic NPs

• shows improved RNA delivery efficiency and overcomes the obstacles of body clearance, insufficient targeting, and low biocompatibility [115]. PLGA NPs loaded with siRNA-E7 and PTX were synthesized for cervical cancer treatment. siRNA-E7 enables the knockdown of E7, which leads to upregulation of the

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

• synergistic effects, and (iv) cytotoxic or molecular targeting agents with small interfering RNA (siRNA) for silencing the mutating genes at protein and messenger RNA (mRNA) level, have made their way to clinical therapy or are under evaluation for their efficacy and safety in many research studies and

• the limitations of the conjugates [68][69]. Cytotoxic or molecular targeting agents with siRNA Targeting homologous mRNA sequences in cells and knockdown of receptors involved in cell survival and proliferation using RNA interference downregulates receptor protein expression, inhibits cell growth, and

• induces apoptosis. The effect obtained by siRNA is not influenced by the receptor alteration status and significantly decreases the gene's oncogenic potential. Chen et al. compared the efficacy of TKIs in NSCLC cells harboring different mutations with combined therapy consisting of TKIs (gefitinib

Cyclodextrins as eminent constituents in nanoarchitectonics for drug delivery systems

• Makoto Komiyama

Beilstein J. Nanotechnol. 2023, 14, 218–232, doi:10.3762/bjnano.14.21

• nanoarchitectures are highly promising for future applications in medicine, pharmaceutics, and other relevant fields. Keywords: cyclodextrin; drug delivery system (DDS); nanoarchitecture; phototherapy; siRNA; Review 1 Introduction Recently, drug delivery systems (DDSs) have been attracting much interest [1][2][3

• nucleic acids are RNAs, DNAs, and derivatives thereof that regulate the expression of target genes [57][58][59]. Typical examples are antisense DNA, small interfering RNA (siRNA), aptamers, and ribozymes/DNAzymes. Owing to the accurate targeting at pathogenic genes, they are promising for various

• resultant well-organized orientation of functional groups in CyD-based nanoarchitectures, should be very appropriate to yield both stable encapsulation of nucleic acid drugs and their prompt release when needed. 3.1 CyD-based nanoarchitectures for delivery of siRNA The therapeutic nucleic acid siRNA is

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

• recently due to a very weak luminescence. Lin et al. synthesized mostly linear PEI and demonstrated a siRNA delivery with this luminescent polymer [27]. Sun et al. utilized the luminescence of branched PEI as the imaging modality in polymeric quantum dots (PDOTs) formed from amphiphilic polyethyleneimine

An overview of microneedle applications, materials, and fabrication methods

• Zahra Faraji Rad,
• Philip D. Prewett and
• Graham J. Davies

Beilstein J. Nanotechnol. 2021, 12, 1034–1046, doi:10.3762/bjnano.12.77

• wafer is anodically bonded to a silicon wafer with predefined cavities (Figure 3) [66]. Deng et al. produced a solid pyramidal silicon microneedle array for in vivo delivery of the cholesterol-modified housekeeping gene siRNA to mice ear skin. The microneedles were 200 μm in height with a tip radius of

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

• arrest, demonstrating a sensitiveness of the cells to nilotinib that is attributable to IM. Mendonca and co-workers worked on developing a targeted NDDS for а combination of siRNA and TKI in CML treatment [63]. The authors developed sterically stabilized liposomes decorated with transferrin for co

• -delivery of siRNA and IM for specifically silencing the BCR-ABL oncogene. In this case, IM enables the pre-sensitization of tumor cells, as a prerequisite for effective gene silencing, mediated by the siRNA. The results demonstrate that the siRNA/IM ratio affected the efficacy in BCR-ABL silencing and

• higher levels of transferrin receptor expression and lower BCR-ABL mRNA levels were more sensitive to the prepared liposomal formulation. The importance of co-delivery of both agents was also observed as lower siRNA/imatinib ratios were needed to achieve IC50 values equivalent to those of the experiments

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

• with polyethyleneimine and conjugated with CD44 siRNA can be used as non-viral gene therapy vectors. Polyethylene imine is the material of choice for nucleic acid intracellular delivery, as it gives a positive charge to the nanoparticle surface [41]. Polyvinyl alcohol (PVA)-coated SPIONs were tested as

Multilayer capsules made of weak polyelectrolytes: a review on the preparation, functionalization and applications in drug delivery

• Varsha Sharma and
• Anandhakumar Sundaramurthy

Beilstein J. Nanotechnol. 2020, 11, 508–532, doi:10.3762/bjnano.11.41

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

• effects on tumor cells in vitro. However, only BMV did not activate macrophages in vitro. This suggests that BMV is less immunogenic and may be a potential carrier for therapy delivery in tumor cells. Furthermore, BMV virus-like particles (VLPs) were efficiently loaded with small interfering RNA (siRNA

• chlorotic mottle virus (CCMV); nanocarriers; plant virus-like particles (VLPs); siRNA delivery; small interfering RNA (siRNA); Introduction Despite many efforts taken, the efficient and specific delivery of therapeutic molecules to tumor cells is still a unsolved challenge. Cancer therapies are often

• the capsid [25][27]. Similarly, VLPs from the closely related cowpea chlorotic mottle virus (CCMV) have been loaded with different cargos, including gold nanoparticles, negatively charged chromophores, and polymers [22]. Small interfering RNA (siRNA) is a promising therapeutic solution to address gene

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

• Russian Academy of Sciences, 3, Ulan-Batorskaya St., P.O. Box 278, Irkutsk, 664033, Russia 10.3762/bjnano.11.26 Abstract The present work explores the ability of poly(1-vinylimidazole) (PVI) to complex small interfering RNA (siRNA) silencing vascular endothelial growth factor (VEGF) and the in vitro

• internalization and escaped the endosome effectively. The polyplex was more effective than free siRNA in silencing VEGF in lung cancer cells. The silencing of VEGF was quantified using Western blot and was also reflected in the depletion of HIF-1α levels in the cells treated with the polyplex. VEGF silencing by

• the polyplex was found to augment the cytotoxic effects of the chemotherapeutic agent 5-fluorouracil. Microarray analysis of the mRNA isolated from cells treated with free siRNA and the polyplex reveal that the VEGF silencing by the polyplex also altered the expression levels of several other genes

Molecular architectonics of DNA for functional nanoarchitectures

• Debasis Ghosh,
• Lakshmi P. Datta and
• Thimmaiah Govindaraju

Beilstein J. Nanotechnol. 2020, 11, 124–140, doi:10.3762/bjnano.11.11

• -functionalized iron oxide nanoparticle system was capable of selectively targeting the cancer cells and, potentially, to act as an MRI contrast agent. The programmability of the DNA tetrahedrons provided an opportunity to conjugate other functional nucleic acid sequences, viz., DNA, siRNA, or DNAzymes, to serve

• co-workers showed that self-assembled DNA tetrahedron nanoarchitectures with narrow size distribution could deliver siRNA into tumor cells [71]. The programmable DNA strands were functionalized with tumor-targeting folate ligands. The nanoarchitecture consisted of six DNA strands having a total of

• was exactly complementary to the siRNA sequence, and, typically, six siRNAs could be annealed with the tetrahedron unit. To ascertain the in vivo transfection efficiency of the siRNA-loaded DNA tetrahedron nanoarchitecture, pharmacokinetic profiling and organ biodistribution assays were conducted in

Internalization mechanisms of cell-penetrating peptides

• Ivana Ruseska and
• Andreas Zimmer

Beilstein J. Nanotechnol. 2020, 11, 101–123, doi:10.3762/bjnano.11.10

• peptide nucleic acids (PNAs) and phosphorodiamidate morpholino oligonucleotides (PMOs) [3][12]. Concerning charged molecules such as siRNA or miRNA, the covalent conjugation leads to restricted biological activity, most likely due to the steric hindrance caused by the covalently-linked CPP, which is an

• obstacle for the incorporation of siRNA/miRNA into the RISC complex. Because of this, the siRNA/miRNA molecule cannot be loaded into the complex and manifest its effect [13]. Regarding covalent strategies of cargo-attachment, there is a great promise in biorthogonal chemistry, which allows for the design

• -siRNA/miRNA delivery [17]. It has been reported that CPP-siRNA conjugates have reduced transient and stable expression of reporter transgenes in a number of mammalian cell lines [18]. In this case, thiol-containing siRNAs were synthesized and conjugated to penetratin or transportan by a reducible