Toxicity of Polymeric-Based Non-Viral Vector Systems for Pulmonary siRNA Application

Beyerle, Andrea; Kissel, Thomas; Stoeger, Tobias

doi:10.5772/22166

Cited by 2 publications

(3 citation statements)

References 118 publications

(131 reference statements)

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“…13−15 However, their low transfection efficacy compared to viral vectors and structure-dependent cytotoxicity limit their wide therapeutic applications. 9 Therefore, the search of new and more effective CPs as gene carriers remains topical.…”

Section: ■ Introductionmentioning

confidence: 99%

“…CPs have also attracted keen attention because of their lower safety risks and ability to interact with cells effectively. − Carefully designed CPs easily form complexes with negatively charged nucleic acids, condensing them into nano-sized structures. − However, their low transfection efficacy compared to viral vectors and structure-dependent cytotoxicity limit their wide therapeutic applications . Therefore, the search of new and more effective CPs as gene carriers remains topical.…”

Section: Introductionmentioning

confidence: 99%

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Library of Cationic Polymers Composed of Polyamines and Arginine as Gene Transfection Agents

et al. 2019

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Combinatorially synthesized materials, especially cationic polymers (CPs), with gene transfection function hold great promise in nanotechnology. However, the main limitations of the existing CPs [such as polyethylenimine (PEI), poly-L-arginine, or polyamidoaminebased dendrimers] as gene transfection agents are high cytotoxicity in the physiological environment. We have developed novel CPs composed of polyaminesendogeneous tetraamine spermine (Spm) and synthetically made triamine N-(2-aminoethyl)-1,3-propanediamine (Apd) for incorporating sec-amino groups and imparting PEI-like structure to the CP backbones. Naturally occurring building blocks such as amino acid arginine (R) was also used for incorporating guanidine-groups into the CPs. The cytotoxicity of resulting CPspolyureas (PUs) and polyamides such as polysuccinamides and R-attached polymalamides was evaluated using murine and human fibroblasts and carcinoma cell lines. The cell compatibility screening revealed that the CPs made of Apd are less cytotoxic compared to Spm-based analogues. From the novel polymer library, total of six polymers were further studied for oligonucleotide (pDNA) complexation and transfection abilities. Highly water-soluble CPs formed nano-sized polyplexes with pDNA at rather low CP/pDNA weight ratios and showed less cytotoxicity and higher transfection ability compared to widely used PEI as well as commercially available transfection agents. Furthermore, new CPs showed selective transfection activity toward certain cell lines (4T1, HeLa, NIH3T3, and CCD 27SK), which is important for their potential applications in gene therapy.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Library of Cationic Polymers Composed of Polyamines and Arginine as Gene Transfection Agents

et al. 2019

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“…The major benefit of using such synthetic vectors is their ability to complex and deliver large quantities of nucleic acids of virtually any size, and they are also generally considered to be safer than viral vectors. − The therapeutic applications of such nonviral gene delivery systems are still rather limited. The major limitations of synthetic polymers compared to viral-based carriers are their relatively low transfection efficiency and high cytotoxicity, − and the latter is the main focus of our work.…”

Section: Introductionmentioning

confidence: 99%

Arginine-Based Biodegradable Ether–Ester Polymers with Low Cytotoxicity as Potential Gene Carriers

et al. 2014

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The success of gene therapy depends on safe and effective gene carriers. Despite being widely used, synthetic vectors based on poly(ethylenimine) (PEI), poly(l-lysine) (PLL), or poly(l-arginine) (poly-Arg) are not yet fully satisfactory. Thus, both improvement of established carriers and creation of new synthetic vectors are necessary. A series of biodegradable arginine-based ether-ester polycations was developed, which consists of three main classes: amides, urethanes, and ureas. Compared to that of PEI, PLL, and poly-Arg, much lower cytotoxicity was achieved for the new cationic arginine-based ether-ester polymers. Even at polycation concentrations up to 2 mg/mL, no significant negative effect on cell viability was observed upon exposure of several cell lines (murine mammary carcinoma, human cervical adenocarcinoma, murine melanoma, and mouse fibroblast) to the new polymers. Interaction with plasmid DNA yielded compact and stable complexes. The results demonstrate the potential of arginine-based ether-ester polycations as nonviral carriers for gene therapy applications.

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Toxicity of Polymeric-Based Non-Viral Vector Systems for Pulmonary siRNA Application

Cited by 2 publications

References 118 publications

Library of Cationic Polymers Composed of Polyamines and Arginine as Gene Transfection Agents

Library of Cationic Polymers Composed of Polyamines and Arginine as Gene Transfection Agents

Arginine-Based Biodegradable Ether–Ester Polymers with Low Cytotoxicity as Potential Gene Carriers

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