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

• overview of the current status and outline important concerns regarding the need for standardized protocols to evaluate NP uptake, NP transfection efficacy, drug dose determination, and variability of nonviral gene delivery systems. Based on these concerns, we propose wide adherence to multimodal

• field of nonviral gene delivery. Keywords: characterization; dosage; gene delivery; uptake; transfection; Introduction Recent efforts to develop and translate therapeutically loaded nanoparticles (NPs) have resulted in several advances in the treatment and prevention of disease. Key areas where NP

• due to the COVID-19 pandemic and the breathtaking acceptance of mRNA-based vaccines [15]. Following the spirit of MIRIBEL, the current perspective was written with two specific aims in mind. First is to provide an overview of current concerns regarding aspects of NP uptake, transfection efficiencies

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

• targeting Renilla luciferase mRNA. Gene inhibition showed an optimum efficiency (40%) at a given nanoparticle/antisense oligonucleotide ratio, which is promising for in vitro cell transfection. When water was replaced with PBS (0.16 M) for the PIC preparation of nanoemulsions starting from

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

• antigen further induces antitumor immunity in the body through presentation [81]. This tumor treatment strategy has shown promise due to its noninvasiveness and specific selectivity. 4.4 Gene therapy Gene therapy can modulate tumorigenesis and progression by delivering transfection-related components to

• major organs [115]. miRNA365 has been confirmed to inhibit tumor cell development and promote tumor cell apoptosis in the colon and other tumors [116]. Zhang et al. achieved efficient gene transfection in tumor tissue by preparing homologous colon cancer membrane-coated biomimetic NPs [55]. These

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

• lipid carriers based on ionizable lipids with pKa values between 6 and 7. OnpattroTM is the first RNAi therapy used for liver-based gene silencing approved by the FDA and EC and is a SNALP transfection system based on transient PEGylation. The lipid components of these benchmark LNPs for siRNA and mRNA

• payload into the cytoplasm and efficacious transfection [142][143][144][145][146][147][148]. Besides the efforts for liver and liver hepatocyte targeting, different research groups are working on the challenge of developing lipid nanoparticles for specific organ targeting after IV administration

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

• applications. However, nucleic acids are intrinsically unstable in serum and do not readily cross the cellular plasma membranes. Accordingly, it is a big challenge to deliver them in the intact form into target cells. Conventional gene transfection reagents are not very good candidates, since multiple positive

• charges of high density can damage the membranes and organelles of normal cells. With the use of CyD-based DDSs, however, high transfection efficiency and low cytotoxicity have been accomplished with minimal immune stimulation. The preorganized three-dimensional molecular structure of CyD as well as the

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

• that the transfection efficiency of cationized gelatin nanoparticles to myeloid leukemia cells (K562) highly depends on the elasticity [16]. Furthermore, it could be shown that stiffer particles were taken up faster in the alveolar epithelial cancer cell line A549 compared to their soft counterparts

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

• , Uskudar, Istanbul, Turkey Koc University, Graduate School of Materials Science and Engineering, Rumelifeneri Yolu, Sariyer, Istanbul, Turkey 10.3762/bjnano.13.6 Abstract Polyethylenimine (PEI), which is frequently used for polyplex formation and effective gene transfection, is rarely recognized as a

• partial PEI oxidation during the synthesis. Here, we demonstrate in vitro dye-free optical imaging and successful gene transfection with luminescent SPION@bPEI, which was further modified for receptor-mediated delivery of the cargo selectively to cancer cell lines overexpressing the epidermal growth

• -Erb was used for the delivery of a GFP plasmid wherein the transfection was confirmed by the luminescence of the expressed gene within the transfected cells. Poor GFP expression in MCF7, a slightly better expression in HeLa, and a significant enhancement in the transfection of HCT116 cells proved a

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

• destroyed with a high-intensity burst of US. Thus, they can locally release the loaded drugs and enhance the penetration depth of the therapeutic agents into the targeted tissue via microstreaming and ARF [72][83][126][168]. Microbubbles can improve the efficacy of gene transfection, therapeutic agents, and

Recent progress in magnetic applications for micro- and nanorobots

• Ke Xu,
• Shuang Xu and
• Fanan Wei

Beilstein J. Nanotechnol. 2021, 12, 744–755, doi:10.3762/bjnano.12.58

• -assisted gene transfection. Magnetic MNRs containing nucleic acids were delivered to target cells by magnetic fields. This method could change gene function or protein expression, which is of great significance for future research on gene transfer and gene therapy. Table 1 summarizes the relevant

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

Cardiomyocyte uptake mechanism of a hydroxyapatite nanoparticle mediated gene delivery system

• Hiroaki Komuro,
• Masahiro Yamazoe,
• Kosuke Nozaki,
• Akiko Nagai and
• Tetsuo Sasano

Beilstein J. Nanotechnol. 2020, 11, 1685–1692, doi:10.3762/bjnano.11.150

• gene delivery systems aimed at penetrating specific target cells, we focused on safe and non-viral gene delivery materials with a high transfection efficiency. Although various techniques have been developed, the mechanisms underlying the cellular uptake of gene delivery materials have not yet been

• vector for transfecting cardiomyocyte-derived HL-1 cells. HAp exhibited particles on the nanoscale and with a low cytotoxicity in HL-1 cells. The transfection assay performed with several endocytosis inhibitors suggested that the HAp/pDNA complexes were internalized by HL-1 cells through macropinocytosis

• advantages in using CaP for gene delivery, the transfection efficiency of CaP/DNA is relatively low according to various preparation parameters [10]. In particular, particle aggregation needs to be improved in order to reduce cellular uptake through the endocytic pathway. Hydroxyapatite (HAp, Ca10(PO4)6(OH)2

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

• microscopy (EM), iron oxide magnetic beads for the separation of cells and molecules, gold and silver nanoparticles as fiducials for EM, for immuno-EM labeling and surface-enhanced Raman spectroscopy, or for gene transfection, liposomes for drug delivery, and gadolinium or iron oxide nanoparticles for

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

• efficiency in cell transfection without inducing in vitro immunological responses when compared with CCMV. In addition, the efficient synthesis of icosahedral BMV VLP-siRNA and its ability to release the small interference RNA molecules into tumor cells was also demonstrated. Thus, the BMV capsids are a

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

• be realized completely due to the challenges associated with stability, target specificity and transfection [1]. The use of viral or non-viral vectors to deliver the therapeutic oligonucleotide to the target cell has been widely explored to overcome the inherent problems associated with the

• administration of the naked oligonucleotide [2]. The majority of gene delivery studies have employed viral vectors due to their superior transfection capabilities. But the high frequency of mutations and packing limitations associated with viral vectors necessitate the search for safer alternatives [3]. In this

• 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

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

• subcellular localization was monitored. An organelle-staining study indicated the localization of the tetrahedrons within the cytoplasm and demonstrated efficient cellular uptake of DNA tetrahedrons without the need for any transfection agents or procedures. One of the advantages of DNA tetrahedrons is that

• 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

• nanoarchitectures and cation-free gene transfection ability. Small-molecule-templated DNA nanoarchitectures The molecular self-assembly of DNA through sequence-specific base pairing is extensively used to create complex nanoarchitectures with variable size and shape in the field of classical DNA nanotechnology. 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

The different ways to chitosan/hyaluronic acid nanoparticles: templated vs direct complexation. Influence of particle preparation on morphology, cell uptake and silencing efficiency

• Arianna Gennari,
• Julio M. Rios de la Rosa,
• Erwin Hohn,
• Maria Pelliccia,
• Enrique Lallana,
• Roberto Donno,
• Annalisa Tirella and
• Nicola Tirelli

Beilstein J. Nanotechnol. 2019, 10, 2594–2608, doi:10.3762/bjnano.10.250

• transfection. Cells were incubated for 4 h with the nanoparticles, then medium was discarded and cells were washed with PBS, and further incubated with 0.25 mL of complete medium for 24 h. Finally, cells were washed with PBS and lysed with Glo-lysis buffer (10 min, 25 °C). The luciferase activity was measured

Long-term stability and scale-up of noncovalently bound gold nanoparticle-siRNA suspensions

• Anna V. Epanchintseva,
• Julia E. Poletaeva,
• Dmitrii V. Pyshnyi,
• Elena I. Ryabchikova and
• Inna A. Pyshnaya

Beilstein J. Nanotechnol. 2019, 10, 2568–2578, doi:10.3762/bjnano.10.248

• corresponding physicochemical characteristics of the suspension. The increase in the volume of the reaction mixture may seem insignificant; however, this technique allowed us to use only one sample for transfection of 1,600,000 cells. Obviously, the use of the same sample of the preparation reduces the

Bombesin receptor-targeted liposomes for enhanced delivery to lung cancer cells

• Mohammad J. Akbar,
• Pâmela C. Lukasewicz Ferreira,
• Melania Giorgetti,
• Leanne Stokes and
• Christopher J. Morris

Beilstein J. Nanotechnol. 2019, 10, 2553–2562, doi:10.3762/bjnano.10.246

• . Samples were incubated at 4, 25 or 37 °C. After 0, 24 and 72 hours the samples were transferred to cuvettes and measured for size and PDI as described above. Cell culture and transfection The adherent, non-small cell cancer cell line A549 was stably transfected with a plasmid encoding HA epitope-tagged

Microbubbles decorated with dendronized magnetic nanoparticles for biomedical imaging: effective stabilization via fluorous interactions

• Da Shi,
• Justine Wallyn,
• Dinh-Vu Nguyen,
• Francis Perton,
• Delphine Felder-Flesch,
• Sylvie Bégin-Colin,
• Mounir Maaloum and
• Marie Pierre Krafft

Beilstein J. Nanotechnol. 2019, 10, 2103–2115, doi:10.3762/bjnano.10.205

• phospholipids allowed for the preparation of MBs that enabled transfection of neuroblastoma cells with a generic, fluorescent, small, interfering RNA under magnetic and ultrasound fields [26]. In the present work, we incorporated IONPs coated by dendritic phosphonates bearing oligo(ethylene glycol) (OEG) chains

Layered double hydroxide/sepiolite hybrid nanoarchitectures for the controlled release of herbicides

• Ediana Paula Rebitski,
• Margarita Darder and
• Pilar Aranda

Beilstein J. Nanotechnol. 2019, 10, 1679–1690, doi:10.3762/bjnano.10.163

• components in diverse electrochemical devices (such as supercapacitors, sensors, and biosensors), in drug delivery and controlled-release formulations, or in non-viral gene transfection [21][22][23][24][25][26]. The fact that the stability of LDH varies with the pH value has proved advantageous in some of

Characterization and influence of hydroxyapatite nanopowders on living cells

• Przemyslaw Oberbek,
• Tomasz Bolek,
• Adrian Chlanda,
• Seishiro Hirano,
• Sylwia Kusnieruk,
• Julia Rogowska-Tylman,
• Ganna Nechyporenko,
• Viktor Zinchenko,
• Wojciech Swieszkowski and
• Tomasz Puzyn

Beilstein J. Nanotechnol. 2018, 9, 3079–3094, doi:10.3762/bjnano.9.286

• regenerative medicine. The use of nanosized hydroxyapatites in biomedical applications is constantly growing due to their good mechanical properties and enhanced efficiency of gene transfection in drug delivery. Calcium phosphates are sensitive to the preparation conditions [11][12][13][14][15]. They can be

• delivery or more effective gene transfection based on hydroxyapatite. The degree of crystallinity can be a factor in determining how long an agglomerate will stay inside the cell and what will be the drug-release rate. Hydroxyapatites with exceptionally large surface area could be also used for

Cytotoxicity of doxorubicin-conjugated poly[N-(2-hydroxypropyl)methacrylamide]-modified γ-Fe₂O₃ nanoparticles towards human tumor cells

• Zdeněk Plichta,
• Yulia Kozak,
• Rostyslav Panchuk,
• Viktoria Sokolova,
• Matthias Epple,
• Lesya Kobylinska,
• Pavla Jendelová and
• Daniel Horák

Beilstein J. Nanotechnol. 2018, 9, 2533–2545, doi:10.3762/bjnano.9.236

• from MRI contrast agents to drug-delivery systems, local heat sources in magnetic hyperthermia therapy of tumors, magnetically assisted transfection of cells, and magnetic field-assisted separation techniques. Let us to note that MRI is already widely used in human medicine and several iron-oxide-based

Non-agglomerated silicon–organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties

• Asya S. Levina,
• Marina N. Repkova,
• Nadezhda V. Shikina,
• Zinfer R. Ismagilov,
• Svetlana A. Yashnik,
• Dmitrii V. Semenov,
• Yulia I. Savinovskaya,
• Natalia A. Mazurkova,
• Inna A. Pyshnaya and
• Valentina F. Zarytova

Beilstein J. Nanotechnol. 2018, 9, 2516–2525, doi:10.3762/bjnano.9.234

• , and to protect DNA against intracellular nucleases [5][6]. The prospect of using SiO2 nanoparticles as nonviral nanovectors to deliver plasmid DNA and their lower toxicity compared to the widely used transfection agent lipofectamine was shown in previous work [6]. It was demonstrated that SiO2

Nanoparticle delivery to metastatic breast cancer cells by nanoengineered mesenchymal stem cells

• Liga Saulite,
• Karlis Pleiko,
• Ineta Popena,
• Dominyka Dapkute,
• Ricardas Rotomskis and
• Una Riekstina

Beilstein J. Nanotechnol. 2018, 9, 321–332, doi:10.3762/bjnano.9.32

• ’-dioctadecyloxacarbocyanine perchlorate (DiO), calcein, PKH67 and baculovirus gene transfer into mammalian cells (BacMam) transfection lacked cell type- selective specificity (data not shown). Thus, we used CD90 as a selective marker for MSCs because it is not expressed on MCF7 and MDA-MB-231 cells [23]. Additionally, we