scholarly journals Thermoresponsive Polyoxazolines as Vectors for Transfection of Nucleic Acids

Polymers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 2609
Author(s):  
Emi Haladjova ◽  
Stanislav Rangelov ◽  
Christo Tsvetanov
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Degree Of Polymerization ◽  
Viral Gene ◽  
Copolymer Composition ◽  
Degree Of Hydrolysis ◽  
Stimuli Responsive ◽  
State Of Research ◽  
Biological Performance

Poly(2-oxazoline)s (POx) are an attractive platform for the development of non-viral gene delivery systems. The combination of POx moieties, exhibiting excellent biocompatibility, with DNA-binding polyethyleneimine (PEI) moieties into a single copolymer chain is a promising approach to balance toxicity and transfection efficiency. The versatility of POx in terms of type of substituent, copolymer composition, degree of polymerization, degree of hydrolysis, and chain architecture, as well as the introduction of stimuli-responsive properties, provides opportunities to finely tune the copolymer characteristics and physicochemical properties of the polyplexes to increase the biological performance. An overview of the current state of research in the POx–PEI-based gene delivery systems focusing particularly on thermosensitive POx is presented in this paper.

scholarly journals Nanoparticle-Mediated Interleukin-12 Cancer Gene Therapy

2010 ◽  
Vol 13 (3) ◽  
pp. 472 ◽  
Author(s):  
Crispin Dass ◽  
Somayeh Hallaj-Nezhadi ◽  
Farzaneh Lotfipour
Keyword(s):  
Gene Delivery ◽  
Viral Vectors ◽  
Safety Concern ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Interleukin 12 ◽  
Viral Gene ◽  
Tumor Site ◽  
Antitumor Effects ◽  
Strong Immune Response

Interleukin-12 (Il-12) is a heterodimeric cytokine which has been proved to possess antitumor effects in various animal models via stimulating the immune system. The main problem associated with Il-12 protein delivery is its instability as well as cytotoxicity subsequent to systemic administration in rodents and in human clinical trials. However, gene delivery can be used to deliver genes of interest to the tumor site. Hence, a large number of studies have been undertaken to deliver genes of interest to the tumor site through viral or non-viral vectors. Viral DNA delivery systems suffer from safety concern due to the toxicity of the viruses and strong immune response; while non-viral gene delivery systems proffer lower transfection efficiency. Nevertheless, nanometer-size complex of therapeutic DNA may demonstrate more efficient for administration of therapeutic genes to solid tumors compared to administration of naked plasmid DNA. Nanoparticle-based gene delivery systems might be more pertinent, due to the enhanced tissue penetrability, improved cellular uptake. Il-12 gene delivery has already been reported with different nanoparticles containing DNA. This article provides a review on the in vivo and in vitro studies using various nanoparticles, for delivery of the Il-12 genes to neoplastic cells. The future of these promising approaches lies in the development of better techniques for preparing il-12 gene delivery systems with complete efficiency of viral vectors in addition to the highest safety for cancer patients.

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.

Chitosan nanoparticles as non-viral gene delivery systems: Determination of loading efficiency

2014 ◽  
Vol 68 (6) ◽  
pp. 775-783 ◽  
Author(s):  
Carolina Carrillo ◽  
Josep Maria Suñé ◽  
Pilar Pérez-Lozano ◽  
Encarna García-Montoya ◽  
Rocío Sarrate ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Chitosan Nanoparticles ◽  
Delivery Systems ◽  
Viral Gene ◽  
Loading Efficiency ◽  
Viral Gene Delivery

Flexible cyclic siloxane core enhances the transfection efficiency of polyethylenimine-based non-viral gene vectors

2015 ◽  
Vol 3 (42) ◽  
pp. 8250-8267 ◽  
Author(s):  
Cristina M. Uritu ◽  
Manuela Calin ◽  
Stelian S. Maier ◽  
Corneliu Cojocaru ◽  
Alina Nicolescu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Cyclic Siloxane ◽  
Gene Vectors

cD4H–AGE–PEI conjugates, with a favorable balance between hydrophilic and hydrophobic moieties, are promising carriers for gene delivery.

Receptor-Mediated Gene Delivery Using Chitosan Derivatives In Vitro and In Vivo

2007 ◽  
Vol 342-343 ◽  
pp. 449-452 ◽  
Author(s):  
Tae Hee Kim ◽  
Hua Jin ◽  
Hyun Woo Kim ◽  
Myung Haing Cho ◽  
Jae Woon Nah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Viral Gene ◽  
Gene Delivery System ◽  
Targeted Gene Delivery ◽  
Cell Specificity ◽  
Selective Delivery

The key strategy for the advancement of gene therapy is the development of an efficient targeted gene delivery system into cells. The targeted gene delivery system is especially important in non-viral gene transfer which shows the relatively low transfection efficiency. It also opens the possibility of selective delivery of therapeutic plasmids to specific tissues. Chitosan has been considered to be a good candidate for gene delivery system, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low specificity and low transfection efficiency of chitosan need to be overcome prior to clinical trial. In this study, we focused on the chemical modification of chitosan for enhancement of cell specificity and transfection efficiency. Also, the potential of clinical application was investigated.

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