Amino Acid-Modified Polyethylenimines with Enhanced Gene Delivery Efficiency and Biocompatibility

Zhang, Qinfang; Luan, Chaoran; Yin, Dali; Zhang, Ji; Liu, Yanhong; Pan, Qi; Xu, Yongjian; Yu, Xiao‐Qi

doi:10.3390/polym7111516

Cited by 16 publications

(13 citation statements)

References 40 publications

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“…As expected from DNA complexation results, and as often reported for bPEI derivatives [29][30][31], the degree of substitution strongly influenced the transfection properties. Very high substitution degrees led to low efficiency (PEI2-St12, PEI2-LA9, PEI1.2-αLA6) both in PAoSMCs and HUASMCs.…”

Section: Transfection Of Vsmcs By Bpei Derivativessupporting

confidence: 74%

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

et al. 2017

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Gene therapy targeted to vascular cells represents a promising approach for prevention and treatment of pathological conditions such as intimal hyperplasia, in-stent and post-angioplasty restenosis. In this context, polymeric non-viral gene delivery systems are a safe alternative to viral vectors but a further improvement in efficiency and cytocompatibility is needed to improve their clinical success. Herein, a library of 24 branched polyethylenimine (bPEI) derivatives modified with hydrophobic moieties was synthesised, characterised and tested in vitro on primary vascular cells, aiming to identify delivery agents with superior transfection efficiency and low cytotoxicity. Low molecular weight PEIs (0.6, 1.2 and 2 kDa) were grafted with long (C18) and short (C3) aliphatic chains, featuring different unsaturation degrees and degrees of substitution. 0.6 kDa bPEI-based derivatives were generally ineffective in transfection on vascular smooth muscle cells (VSMCs), while among the other derivatives some promising vectors were identified. Forcing polyplexes on the cell surface by means of centrifugation invariably boosted transfection levels but increased cytotoxicity as well. Of note, a propionyl-substituted derivative (PEI2-PrA1, C3:0) was the most effective on both VSMCs and endothelial cells (ECs), with higher and more sustained gene expression in combination with markedly lower cytotoxicity with respect to the gold standard 25 kDa bPEI. In addition, a linoleoyl-substituted derivative (PEI1.2-LA6, C18:2) owing to its high efficiency in VSMCs and relative inefficacy in ECs, combined with tolerable cytotoxicity was proposed as a vector for specific VSMCs targeting.

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Section: Transfection Of Vsmcs By Bpei Derivativessupporting

confidence: 74%

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

et al. 2017

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“…For instance, it was found, when PEI was modified with amino acids, the transfection efficiency and biocompatibility could be further improved. Glycolic acid-grafted PEI was able to achieve 23 times higher luciferase gene expression [164] than PEI alone. When PEI (MW 800 Dalton) was used to coat nanodiamond, the gene expression increased 70 times in comparison with PEI alone [165].…”

Section: Discussionmentioning

confidence: 97%

Current and future technological advances in transdermal gene delivery

Chen

2018

Advanced Drug Delivery Reviews

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Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the "bricks-and-mortar" structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided.

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“…While these effects may be favorable in the trafficking and permeability of membranes to nucleic acid polyplexes, they ultimately limit cellular viability and potential translation. There have been many advances toward improving the cytotoxicity of cationic polymers, especially PEI, that include modification with amino acids, sugars, lipids, and polymers …”

Section: Design Considerations In Engineering Hydrogels For Rnai Delimentioning

confidence: 99%

Engineered Hydrogels for Local and Sustained Delivery of RNA‐Interference Therapies

Wang

Burdick

2016

Adv Healthcare Materials

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It has been nearly two decades since RNA-interference (RNAi) was first reported. While there are no approved clinical uses, several promising phase II and III clinical trials suggest the great promise of RNAi therapeutics. One challenge for RNAi therapies is the controlled localization and sustained presentation to target tissues, to both overcome systemic toxicity concerns and to enhance in vivo efficacy. One approach that is emerging to address these limitations is the entrapment of RNAi molecules within hydrogels for local and sustained release. In these systems, nucleic acids are either delivered as siRNA conjugates or within nanoparticles. A plethora of hydrogels has been implemented using these approaches, including both traditional hydrogels that have already been developed for other applications and new hydrogels developed specifically for RNAi delivery. These hydrogels have been applied to various applications in vivo, including cancer, bone regeneration, inflammation and cardiac repair. This review will examine the design and implementation of such hydrogel RNAi systems and will cover the most recent applications of these systems.

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Amino Acid-Modified Polyethylenimines with Enhanced Gene Delivery Efficiency and Biocompatibility

Cited by 16 publications

References 40 publications

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

Current and future technological advances in transdermal gene delivery

Engineered Hydrogels for Local and Sustained Delivery of RNA‐Interference Therapies

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