Gene Delivery by PAMAM Dendrimer Conjugated with the Nuclear Localization Signal Peptide Derived from Influenza B Virus Nucleoprotein

Lee, Jeil; Lee, Seulgi; Kwon, Yong-Eun; Kim, Youn-Joong; Choi, Ji Soo

doi:10.1007/s13233-019-7057-9

Cited by 19 publications

(7 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, polymers are advantageous because they are highly tailorable and have the ability to self-assemble into different shapes [6]. For instance, recent developments have targeted HepG2, and A549 cell lines with polyamidoamine, PC-3 prostate cancer cell line with polyethyleneimine (PEI) plus a polyethyleneglycol (PEG) linker, studies which demonstrate the promising ability of the polymers for delivery purposes [21,22]. Additionally, You et al [23] developed a pH-responsive polymeric system with the ability to not only penetrate cells but deliver a carDNA cargo once it is internalized.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

show abstract

“…To enhance the gene expression efficiency of a 3rd generation PAMAM, surface modification was performed with influenza B virus nucleoprotein lysine-arginine-threonine-arginine peptide as a nuclear localization signal. Lee et al 133 synthesized PAMAM-G3.0-RTRK and PAMAM-G3.0-histidine-arginine-threonine-arginine-lysine (HRTRK) peptides to evaluate the influence of the histidine residue on cytotoxicity. They found that histidine residues could reduce cytotoxicity and allow prolonged gene expression.…”

Section: Histidine-modified Branched Polymersmentioning

confidence: 99%

Histidine‐enhanced gene delivery systems: The state of the art

Hooshmand

Sabet

Hasanzadeh

et al. 2022

The Journal of Gene Medicine

View full text Add to dashboard Cite

Gene therapy has emerged as a promising tool for treating different intractable diseases, particularly cancer or even viral diseases such as COVID-19 (coronavirus disease 2019). In this context, various non-viral gene carriers are being explored to transfer DNA or RNA sequences into target cells. Here, we review the applications of the naturally occurring amino acid histidine in the delivery of nucleic acids into cells.The biocompatibility of histidine-enhanced gene delivery systems has encouraged their wider use in gene therapy. Histidine-based gene carriers can involve the modification of peptides, dendrimers, lipids or nanocomposites. Several linear polymers, such as polyethylenimine, poly-L-lysine (synthetic) or dextran and chitosan (natural), have been conjugated with histidine residues to form complexes with nucleic acids for intracellular delivery. The challenges, opportunities and future research trends of histidine-based gene deliveries are investigated.

show abstract

“…Apart from the partial zwitterion modification-enabled serum-promoted gene delivery performance, PAMAM DE-Au-NPs can be partially modified with targeting ligands to render the gene delivery with desired specificity. With the abundant periphery amines of PAMAM dendrimers, covalent conjugation of various targeting agents including monoclonal antibodies, peptides/proteins, − vitamins, , carbohydrate, or other ligands is possible. Taking two examples, targeting ligands of folic acid (FA) and arginine-glycine-aspartic acid (RGD) peptide have been linked onto the surface of DE-Au-NPs for respective specific gene delivery applications.…”

Section: Strategies To Enhance Gene Delivery Efficiency With Reduced ...mentioning

confidence: 99%

Poly(amidoamine) Dendrimer-Gold Nanohybrids in Cancer Gene Therapy: A Concise Overview

Shen

Shi

2020

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

Nonviral gene delivery has been considered as a powerful tool for cancer therapy because of its inherent advantages of nontoxicity, high specificity, and therapeutic efficacy. Successful cancer gene therapy mostly depends on the design of highly efficient and nontoxic vectors that can compress genetic materials and effectively deliver them to target cells. Dendrimers, in particular, poly(amidoamine) dendrimers with highly branched internal cavities and abundant surface amine groups, have been used as vectors for gene delivery but suffer problems of toxicity, low efficiency, and nonspecificity. Here, we summarize the updated progresses in the design of dendrimer-gold (Au) nanohybrids for improved gene delivery and cancer gene therapy by taking advantage of the unique properties of the integrated Au nanoparticles (AuNPs). In particular, the dendrimer-gold nanohybrids can be partially functionalized with acetyl, polyethylene glycol, and cyclodextrin to reduce their cytotoxicity; decorated with zwitterions to afford serum-enhanced gene delivery; and modified with targeting ligands to be rendered with the gene delivery specificity. A variety of genetic materials including plasmid DNA, small-interfering RNA, microRNA inhibitor, and immunoactivator have been delivered using the designed dendrimer-gold nanohybrids as vectors for effective gene therapy, immunotherapy, and combinational gene/photothermal therapy and gene/chemo therapy. We concisely overview the recent key developments of dendrimer-Au nanohybrids for improved cancer gene therapy and emphasize the role played by the AuNPs to boost the combinational therapy. The challenges and future perspectives regarding this particular area of research are also concisely discussed.

show abstract

Gene Delivery by PAMAM Dendrimer Conjugated with the Nuclear Localization Signal Peptide Derived from Influenza B Virus Nucleoprotein

Cited by 19 publications

References 19 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

Histidine‐enhanced gene delivery systems: The state of the art

Poly(amidoamine) Dendrimer-Gold Nanohybrids in Cancer Gene Therapy: A Concise Overview

Contact Info

Product

Resources

About