Gene delivery of PEI incorporating with functional block copolymer via non-covalent assembly strategy

Hu, Yuling; Zhou, Daohong; Li, Congxin; Zhou, Hao; Chen, Jiatong; Zhang, Zhengpu; Guo, Tianying

doi:10.1016/j.actbio.2012.09.033

Cited by 31 publications

(27 citation statements)

References 39 publications

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“…Ternary DNA complexes have received considerable attention in the field of gene delivery due to either their facile formulations or their capabilities to converge three different components into one macromolecular form such that they can simultaneously possess the various characteristic properties of each element of the ternary complex . Typically, ternary DNA complexes are composed of negatively charged plasmid DNA with two elements: one is usually a macromolecule with cationic charges to form DNA complexes through electrostatic interactions, and the other is a structure or a moiety with additional property.…”

Section: Resultsmentioning

confidence: 99%

“…Typically, ternary DNA complexes are composed of negatively charged plasmid DNA with two elements: one is usually a macromolecule with cationic charges to form DNA complexes through electrostatic interactions, and the other is a structure or a moiety with additional property. Thus, in addition to the property of inducing substantially enhanced delivery efficiency, ternary DNA complexes could also induce synergistic effects in achieving multifunctional performance, including specificity in targeting, lower cytotoxicity, and dual‐delivery of multiple agents . Moreover, these properties could be regarded as crucial features for designing the next generation of gene vectors.…”

Section: Resultsmentioning

confidence: 99%

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Enhanced Cellular Transfection by Ternary Non-Viral Gene Vectors Coupled with Adeno-Associated Virus-Derived Peptides

Park

Kim

et al. 2013

Macromol. Biosci.

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The establishment of efficient and safe gene delivery systems is crucial for biomedical applications. To address this objective, novel, ternary hybrid gene vectors are designed with viral capsid peptides in non-viral gene carriers. The viral peptide, TQVGQKT, is coupled with a membrane active peptide, LK15. Which acts as a linker to tag peptide with plasmid DNA. Additionally, polyethylenimine (PEI) is employed to condense the complexes further, thereby forming ternary DNA/TQVGQKT-LK15/PEI complexes. The ternary complexes result in rapid internalization leading to significantly enhanced cellular transfection. The new moiety, TQVGQKT, as well as enhanced cellular transfection, will certainly provide crucial insights for the design of novel non-viral gene carriers with efficient and safe properties.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Enhanced Cellular Transfection by Ternary Non-Viral Gene Vectors Coupled with Adeno-Associated Virus-Derived Peptides

Park

Kim

et al. 2013

Macromol. Biosci.

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“…The formulation where PEI 10k was complexed with siRNA at an N/P ratio of 50 and further incorporated into 1% (m/v) Pluronic ® F127based PM, presented similar transfection efficacy and GFP silencing than Lipofectamine ® 2000. Contrarily to the need of complex chemical modifications proposed by other studies (62,63), in this work we used a simple association of PEI-based polyplexes with Pluronic ® F127-based PM. The micelles prepared by DM present the great advantage of being prepared by a simpler method, importantly avoiding the use of organic solvents.…”

Section: Discussionmentioning

confidence: 99%

Rational Design of a siRNA Delivery System: ALOX5 and Cancer Stem Cells as Therapeutic Targets

Abasolo

Sayós

Arango

et al. 2018

PRNANO

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The search for an ideal gene delivery system is a long and laborious process in which several factors from the first idea to final formulation, including main challenges, peaks and troughs, should be deeply taken into consideration to ensure adequate biological safety and in vivo efficacy endpoints. Arachidonate 5-lipoxygenase (ALOX5), a crucial player related with cancer development and in particular with cancer stem cells malignancy. In this work we describe the process behind the development of a small interfering RNA (siRNA) delivery system to inhibit ALOX5 in cancer stem cells (CSC), as a model target gene. We started by screening chitosan polyplexes, among different types of chitosan in different complexation conditions. Due to the low silencing efficacy obtained, chitosan polyplexes were combined with Pluronic®-based polymeric micelles with recognized advantages regarding gene transfection. We tested different types of polymeric particles to improve the biological efficacy of chitosan polyplexes. Nevertheless, limited transfection efficiency was still detected. The well-established polyethyleneimine (PEI) cationic polymer was used in substitution of chitosan, in combination with polymeric micelles, originating PEI-siRNA-Pluronic® systems. The presence of Pluronic® F127 in the formulation showed to be of utmost importance because not only the silencing activity of the polyplexes was improved, but also PEI-associated toxicity was clearly reduced. This, allowed to increase the amount of PEI inside the system and its overall efficacy. Indeed, different types of PEI, N/P ratios and preparation methods were tested until an optimal formulation composed by PEI 10k branched-based polyplexes at an N/P ratio of 50 combined with micelles of Pluronic® F127 was selected. This combined micelle presented adequate technological properties, safety profile, and biological efficacy, resulting in high ALOX5 gene silencing and strong reduction of invasion and transformation capabilities of a stem cell subpopulation isolated from MDA-MB-231 triple negative breast cancer cells.

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“…PEI is a synthetic cationic polymer that has been extensively used to deliver oligonucleotides, siRNA, and plasmid DNA in vitro and in vivo [8-10]. Moreover, the cationic charge of the carrier surface can be enhanced through the intracellular uptake of vehicles to negatively charged tumor cells or tissues [11-13].…”

Section: Introductionmentioning

confidence: 99%

Enhanced localization of anticancer drug in tumor tissue using polyethylenimine-conjugated cationic liposomes

et al. 2014

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Liposome-based drug delivery systems hold great potential for cancer therapy. However, to enhance the localization of payloads, an efficient method of systemic delivery of liposomes to tumor tissues is required. In this study, we developed cationic liposomes composed of polyethylenimine (PEI)-conjugated distearoylglycerophosphoethanolamine (DSPE) as an enhanced local drug delivery system. The particle size of DSPE-PEI liposomes was 130 ± 10 nm and the zeta potential of liposomes was increased from -25 to 30 mV by the incorporation of cationic PEI onto the liposomal membrane. Intracellular uptake of DSPE-PEI liposomes by tumor cells was 14-fold higher than that of DSPE liposomes. After intratumoral injection of liposomes into tumor-bearing mice, DSPE-PEI liposomes showed higher and sustained localization in tumor tissue compared to DSPE liposomes. Taken together, our findings suggest that DSPE-PEI liposomes have the potential to be used as effective drug carriers for enhanced intracellular uptake and localization of anticancer drugs in tumor tissue through intratumoral injection.

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Gene delivery of PEI incorporating with functional block copolymer via non-covalent assembly strategy

Cited by 31 publications

References 39 publications

Enhanced Cellular Transfection by Ternary Non-Viral Gene Vectors Coupled with Adeno-Associated Virus-Derived Peptides

Enhanced Cellular Transfection by Ternary Non-Viral Gene Vectors Coupled with Adeno-Associated Virus-Derived Peptides

Rational Design of a siRNA Delivery System: ALOX5 and Cancer Stem Cells as Therapeutic Targets

Enhanced localization of anticancer drug in tumor tissue using polyethylenimine-conjugated cationic liposomes

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