Multifunctional gene delivery systems with targeting ligand CAGW and charge reversal function for enhanced angiogenesis

2019 ◽  
Vol 7 (11) ◽  
pp. 1906-1919 ◽  
Author(s):  
Qiaoping Zhang ◽  
Bin Gao ◽  
Khan Muhammad ◽  
Xubin Zhang ◽  
Xiang-kui Ren ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Endosomal Escape ◽  
Charge Reversal ◽  
Gene Complexes ◽  
Targeting Peptide ◽  
A Charge

A charge reversible polyanion with a targeting peptide was assembled onto binary gene complexes to enhance their endosomal escape and transfection efficiency.

scholarly journals Self-Assembling Multifunctional Peptide Dimers for Gene Delivery Systems

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Kitae Ryu ◽  
Gyeong Jin Lee ◽  
Ji-yeong Choi ◽  
Taewan Kim ◽  
Tae-il Kim
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Weight Ratio ◽  
Delivery Systems ◽  
C2c12 Cells ◽  
Endosomal Escape ◽  
Hek293 Cells ◽  
Matrix Metalloproteinase 2 ◽  
Self Assembling ◽  
Hydrophobic Moiety

Self-assembling multifunctional peptide was designed for gene delivery systems. The multifunctional peptide (MP) consists of cellular penetrating peptide moiety (R8), matrix metalloproteinase-2 (MMP-2) specific sequence (GPLGV), pH-responsive moiety (H5), and hydrophobic moiety (palmitic acid) (CR8GPLGVH5-Pal). MP was oxidized to form multifunctional peptide dimer (MPD) by DMSO oxidation of thiols in terminal cysteine residues. MPD could condense pDNA successfully at a weight ratio of 5. MPD itself could self-assemble into submicron micelle particles via hydrophobic interaction, of which critical micelle concentration is about 0.01 mM. MPD showed concentration-dependent but low cytotoxicity in comparison with PEI25k. MPD polyplexes showed low transfection efficiency in HEK293 cells expressing low level of MMP-2 but high transfection efficiency in A549 and C2C12 cells expressing high level of MMP-2, meaning the enhanced transfection efficiency probably due to MMP-induced structural change of polyplexes. Bafilomycin A1-treated transfection results suggest that the transfection of MPD is mediated via endosomal escape by endosome buffering ability. These results show the potential of MPD for MMP-2 targeted gene delivery systems due to its multifunctionality.

scholarly journals Highly Osmotic Oxidized Sucrose-Crosslinked Polyethylenimine for Gene Delivery Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Jaehong Park ◽  
Kyusik Kim ◽  
Sohee Jeong ◽  
Migyeom Lee ◽  
Tae-il Kim
Keyword(s):  
Gene Delivery ◽  
Reductive Amination ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Buffering Capacity ◽  
Serum Stability ◽  
High Osmolality ◽  
Cox 2 ◽  
Serum Free Conditions ◽  
Positively Charged

In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by 1H NMR and FTIR. The synthesized SP2K polymers could form positively charged (~40 mV zeta-potential) and nano-sized (150–200 nm) spherical polyplexes with plasmid DNA (pDNA). They showed lower cytotoxicity than PEI25K but concentration-dependent cytotoxicity. Among them, SP2K7 and SP2K10 showed higher transfection efficiency than PEI25K in both serum and serum-free conditions, revealing the good serum stability. It was found that SP2K polymers possessed high osmolality and endosome buffering capacity. The transfection experiments with cellular uptake inhibitors suggest that the transfection of SP2K polymers would progress by multiple pathways, including caveolae-mediated endocytosis. It was also thought that caveolae-mediated endocytosis of SP2K polyplexes would be facilitated through cyclooxygenase-2 (COX-2) expression induced by high osmotic pressure of SP2K polymers. Confocal microscopy results also supported that SP2K polyplexes would be internalized into cells via multiple pathways and escape endosomes efficiently via high osmolality and endosome buffering capacity. These results demonstrate the potential of SP2K polymers for gene delivery systems.

Role of charge-reversal in the hemo/immuno-compatibility of polycationic gene delivery systems

2019 ◽  
Vol 96 ◽  
pp. 436-455 ◽  
Author(s):  
Qi Yang ◽  
Shuo Liu ◽  
Xin Liu ◽  
Zonghua Liu ◽  
Wei Xue ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery Systems ◽  
Charge Reversal

NON-CONDENSING POLYMERIC GENE DELIVERY SYSTEMS: PRINCIPLES AND APPLICATIONS

Nano LIFE ◽  
2010 ◽  
Vol 01 (03n04) ◽  
pp. 219-237 ◽  
Author(s):  
SHARDOOL JAIN ◽  
HUSAIN ATTARWALA ◽  
MANSOOR AMIJI
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Contemporary Literature ◽  
Delivery Systems ◽  
Expression Of Genes ◽  
Cytoplasmic Dna ◽  
Polymeric Delivery ◽  
Systemic Gene Delivery

Gene therapy holds tremendous promise in prevention and treatment of diseases as the approach is based on regulating the expression of genes that are responsible for pathological conditions. The biggest bottleneck for gene delivery has been the development of safe and efficacious delivery systems. Although non-viral vectors are considered as much safer options than their viral counterparts, they suffer from low transfection efficiency. In this review, we highlight the role of non-condensing polymeric delivery systems for oral and systemic gene delivery. Using evidence from contemporary literature, non-condensing polymeric microparticle and nanoparticle systems afford physical encapsulation of the nucleic acid construct and can be engineered for targeted delivery to tissues and cells. Additionally, these systems have shown less toxicity and afford sustained cytoplasmic DNA delivery for efficient nuclear uptake and transfection for both DNA vaccines and therapeutic genes.

A dendritic catiomer with an MOF motif for the construction of safe and efficient gene delivery systems

2017 ◽  
Vol 5 (42) ◽  
pp. 8322-8329 ◽  
Author(s):  
Shuqi Dong ◽  
Qixian Chen ◽  
Wei Li ◽  
Zhu Jiang ◽  
Jianbiao Ma ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Gold Standard ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Delivery Systems ◽  
The Core ◽  
Efficient Gene

The dendritic catiomer using biocompatible Zr-MOFs as the core exhibited a markedly higher transfection efficiency and lower cytotoxicity than the commercial gold standard branched PEI25k in A549 cells.

Preparation, characterization and transfection efficiency of cationic PEGylated PLA nanoparticles as gene delivery systems

2007 ◽  
Vol 130 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Jiji Chen ◽  
Buning Tian ◽  
Xiang Yin ◽  
Yanqiong Zhang ◽  
Duosha Hu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Delivery Systems

Peptide amphiphiles with multifunctional fragments promoting cellular uptake and endosomal escape as efficient gene vectors

2015 ◽  
Vol 3 (6) ◽  
pp. 1068-1078 ◽  
Author(s):  
Liang Luan ◽  
Qingbin Meng ◽  
Liang Xu ◽  
Zhao Meng ◽  
Husheng Yan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cellular Uptake ◽  
Transfection Efficiency ◽  
Endosomal Escape ◽  
Peptide Amphiphiles ◽  
Gene Delivery Vectors ◽  
Efficient Gene ◽  
Gene Vectors ◽  
Lipofectamine 2000

A series of peptides containing multiple functional fragments were designed as gene-delivery vectors with transfection efficiency comparable to Lipofectamine 2000.

scholarly journals Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers

2021 ◽  
Vol 9 ◽  
Author(s):  
Ina F. de la Fuente ◽  
Shraddha S. Sawant ◽  
Mark Q. Tolentino ◽  
Patrick M. Corrigan ◽  
Jessica L. Rouge
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Molecular Mechanisms ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Endosomal Escape ◽  
Nucleic Acid Delivery ◽  
Metastable Structure ◽  
Oligonucleotide Delivery ◽  
Genome Protection

Therapeutic nucleic acids hold immense potential in combating undruggable, gene-based diseases owing to their high programmability and relative ease of synthesis. While the delivery of this class of therapeutics has successfully entered the clinical setting, extrahepatic targeting, endosomal escape efficiency, and subcellular localization. On the other hand, viruses serve as natural carriers of nucleic acids and have acquired a plethora of structures and mechanisms that confer remarkable transfection efficiency. Thus, understanding the structure and mechanism of viruses can guide the design of synthetic nucleic acid vectors. This review revisits relevant structural and mechanistic features of viruses as design considerations for efficient nucleic acid delivery systems. This article explores how viral ligand display and a metastable structure are central to the molecular mechanisms of attachment, entry, and viral genome release. For comparison, accounted for are details on the design and intracellular fate of existing nucleic acid carriers and nanostructures that share similar and essential features to viruses. The review, thus, highlights unifying themes of viruses and nucleic acid delivery systems such as genome protection, target specificity, and controlled release. Sophisticated viral mechanisms that are yet to be exploited in oligonucleotide delivery are also identified as they could further the development of next-generation nonviral nucleic acid vectors.

scholarly journals Interaction kinetics of peptide lipids-mediated gene delivery

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

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