Gene delivery by peptide-assisted transport

Thapa, Raj Kumar; Sullivan, Millicent O.

doi:10.1016/j.cobme.2018.10.002

Cited by 28 publications

(11 citation statements)

References 52 publications

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“…Once the nanobioconjugates reached the cytoplasm, a rapid endosomal escape took place, which continued in the case of the SH-SY5Y cells. Several studies report that the cationic properties of Buforin II induce a high osmotic pressure within endosomes, leading to an endosomal breach mediated by a proton sponge effect [76][77][78][79]. The present cationic polymers could have aided this process as they might be likely involved in facilitating the proton sponge effect, as reported elsewhere [80].…”

Section: Cell Translocation and Endosome Escapesupporting

confidence: 67%

PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation

et al. 2020

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Over the past decade, gene therapies have attracted much attention for the development of treatments for various conditions, including cancer, neurodegenerative diseases, protein deficiencies, and autoimmune disorders. Despite the benefits of this approach, several challenges are yet to be solved to reach clinical implementation. Some of these challenges include low transfection rates, limited stability under physiological conditions, and low specificity towards the target cells. An avenue to overcome such issues is to deliver the therapies with the aid of potent cell-penetrating vectors. Non-viral vectors, such as nanostructured materials, have been successfully tested in drug and gene delivery. Here, we propose the development and in vitro evaluation of a nanostructured cell-penetrating vehicle based on core/shell, magnetite/silver nanoparticles. A subsequent conjugation of a pH-responsive polymer was used to assure that the vehicle can carry and release circular DNA. Additionally, the translocating peptide Buforin II was conjugated with the aid of a polyether amine polymer to facilitate translocation and endosome escape. The obtained nanobioconjugates (magnetite/silver-pDMAEMA-PEA-BUFII) were characterized by UV-Vis spectrophotometry, dynamic light scattering (DLS), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope equipped with energy dispersive spectroscopy (SEM+EDS), and transmission electron microscopy (TEM). They were also encapsulated in lecithin liposomes to form magnetoliposomes. The cell viability of Vero cells in the presence of the nanobioconjugates was above 95% and declined to 80% for the magnetoliposomes. The hemolytic tendency of nanobioconjugates and magnetoliposomes was below 10%, while the platelet aggregation approached that of the negative control (i.e., 35%). Cytoplasm coverage values of about 50% for both Vero and neuroblastoma cells confirmed significant cell penetration. Pearson’s correlation coefficients for both cell lines allowed us to estimate 20–40% colocalization of the nanobioconjugates with lysotracker green, which implied high levels of endosomal escape. The developed vehicles were also capable of loading around 16% of the added DNA and releasing such cargo with 8% efficiency. The developed nanoplatform holds a significant promise to enable highly efficient gene therapies as it overcomes some of the major issues associated with their eventual translation to the pre-clinical and clinical scale.

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Section: Cell Translocation and Endosome Escapesupporting

confidence: 67%

PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation

et al. 2020

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“…Peptiplexes are formed via electrostatic interactions between positively charged peptide residues and nucleic acid's negatively charged phosphate backbone. These complexes are compact and stable in nature and have been recognized as efficient carriers in the past years [238,239]. Compared to polyplexes or lipoplexes, peptiplexes offer many advantageous properties such as ease of synthesis at large scales, biocompatibility, stability in case of oxidation, and numerous customization possibilities [240,241].…”

Section: Peptiplexesmentioning

confidence: 99%

Amino Acids, Peptides, and Proteins: Implications for Nanotechnological Applications in Biosensing and Drug/Gene Delivery

Laraib

Arshad

et al. 2021

Nanomaterials

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Over various scientific fields in biochemistry, amino acids have been highlighted in research works. Protein, peptide- and amino acid-based drug delivery systems have proficiently transformed nanotechnology via immense flexibility in their features for attaching various drug molecules and biodegradable polymers. In this regard, novel nanostructures including carbon nanotubes, electrospun carbon nanofibers, gold nanoislands, and metal-based nanoparticles have been introduced as nanosensors for accurate detection of these organic compounds. These nanostructures can bind the biological receptor to the sensor surface and increase the surface area of the working electrode, significantly enhancing the biosensor performance. Interestingly, protein-based nanocarriers have also emerged as useful drug and gene delivery platforms. This is important since, despite recent advancements, there are still biological barriers and other obstacles limiting gene and drug delivery efficacy. Currently available strategies for gene therapy are not cost-effective, and they do not deliver the genetic cargo effectively to target sites. With rapid advancements in nanotechnology, novel gene delivery systems are introduced as nonviral vectors such as protein, peptide, and amino acid-based nanostructures. These nano-based delivery platforms can be tailored into functional transformation using proteins and peptides ligands based nanocarriers, usually overexpressed in the specified diseases. The purpose of this review is to shed light on traditional and nanotechnology-based methods to detect amino acids, peptides, and proteins. Furthermore, new insights into the potential of amino protein-based nanoassemblies for targeted drug delivery or gene transfer are presented.

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“…Influenza-derived, histidine-rich H5WYG peptide that is capable of traversing intracellular barriers to deliver nucleic acids, is another well-known example that raised great interest. This pH sensitive peptide has been extensively applied to improve the gene delivery efficacy of different polymeric, peptidic, and lipid-based carriers [180][181][182][183][184][185][186].…”

Section: Histidine-rich Peptidesmentioning

confidence: 99%

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

Tarvirdipour

Skowicki

Schoenenberger

et al. 2021

IJMS

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Concerns associated with nanocarriers’ therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.

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Gene delivery by peptide-assisted transport

Cited by 28 publications

References 52 publications

PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation

PH-Responsive, Cell-Penetrating, Core/Shell Magnetite/Silver Nanoparticles for the Delivery of Plasmids: Preparation, Characterization, and Preliminary In Vitro Evaluation

Amino Acids, Peptides, and Proteins: Implications for Nanotechnological Applications in Biosensing and Drug/Gene Delivery

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise

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