A strategy to improve serum-tolerant transfection activity of polycation vectors by surface hydroxylation

Luo, Xiao‐Hua; Huang, Farong; Qin, Si‐Yong; Wang, Huafen; Feng, Jie; Zhang, Xian‐Zheng; Zhuo, Ren‐Xi

doi:10.1016/j.biomaterials.2011.09.011

Cited by 87 publications

(84 citation statements)

References 53 publications

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“…[9][10][11] PEI25k, a high molecular weight PEI (25 kDa) typically shows high transgene expression both in vitro and in vivo; however, low biocompatibility and limited stability in the presence of serum have hindered their clinical applications. [12,13] The polyethylenimine (PEI) derivatives (PTn) are prepared by treating PEI25k with Tris-(hydroxymethyl) acrylamidomethane via the Michael addition. These PTns can effectively condense nucleic acids into nanosized particles with positive surface charges.…”

Section: Introductionmentioning

confidence: 99%

A Serum‐Tolerant Hydroxyl‐Modified Polyethylenimine as Versatile Carriers of pDNA/siRNA

Dong

Lin

Chen

et al. 2013

Macromolecular Bioscience

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The polyethylenimine (PEI) derivatives (PTn) are prepared by treating PEI25k with Tris(hydroxymethyl) acrylamidomethane via the Michael addition. These PTns can effectively condense nucleic acids into nanosized particles with positive surface charges. The PTns show lower cytotoxicity and better serum-resistant capacity than PEI25k. Specially, the transfection efficiency of PT26/DNA is 29-fold higher than that of PEI25k in HeLa cells in serum-containing medium. The PTn/siRNA complexes show superior knockdown effect in CT26 cells in serum-containing medium. In addition, flow cytometry analysis shows that the PTns can efficiently mediate the entry of nucleic acids into the cell. Thus, PTns are potentially applicable as non-viral carriers of nucleic acids and warrant further development for use in gene therapy.

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Section: Introductionmentioning

confidence: 99%

A Serum‐Tolerant Hydroxyl‐Modified Polyethylenimine as Versatile Carriers of pDNA/siRNA

Dong

Lin

Chen

et al. 2013

Macromolecular Bioscience

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“…In each cell line, the TE of Ga-PEI was higher than Ser-PEI, which also has hydroxyl groups but maintains the amount of amino groups. This indicates that the balance between electron-positive/negative groups, which also called the "hydroxyl effect" [11,28] or the charge screening effect [29,30], is important for the transfection by such types of polycations, especially in the serum circumstance. On the other hand, Gly-PEI also showed good TE, but the relative TE compared to PEI was lower than that obtained without serum.…”

Section: In Vitro Gene Transfectionmentioning

confidence: 99%

“…This made it the golden standard for the design of novel polymeric vectors [7][8][9]. However, along with the higher TE, significant cytotoxicity and limited biocompatibility are also found in HMW PEI-mediated gene delivery [10,11]. Thus, to develop novel PEI-based materials with both high TE and improved biocompatibility is of great importance.…”

Section: Introductionmentioning

confidence: 99%

“…Ramezani and co-workers revealed that alkyl-oligoamine derivatives of PEI without reduction of primary amine quantity is an effective strategy for the balance of hydrophobic-hydrophilic property and for the improvement of TE while maintaining low toxicity [13]. Zhuo found that the incorporation of a hydroxyl-enriched "skin" would afford PEI-g-5-ethyl-5-(hydroxymethyl)-1,3-dioxan-2-oxo (PEI-g-EHDO) with remarkably improved biocompatibility and stronger resistance against the serum-associated detrimental effects, such as protein adsorption, particle aggregation, and polycation-protein exchange [11]. In addition, poly(ethyleneglycol) (PEG) has been shown to have the ability to shield the positive charges on the complex, improving the serum tolerance [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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Abstract:The development of gene delivery vectors with high efficiency and biocompatibility is one of the key points of gene therapy. A series of polycations were prepared from polyethylenimine (PEI) with several amino acids or their analogs. The target polymers have different charge and hydrophilic/hydrophobic properties, which may affect their performance in the gene transfection process. Gel retardation and DLS assays showed that these polymers may condense DNA into nanoparticles with positive zeta potentials and proper sizes for cellular uptake. Luciferase reporter gene transfection results revealed their higher transfection efficiency than PEI; especially in the presence of serum, in which up to 23 times higher efficiency was achieved by employing glycolic acid-grafted PEI. Moreover, it was found that the degree of substitution on PEI has an apparent influence on the transfection, and the balance between electron-positive/negative groups largely affects the delivery process. The higher serum tolerance was also proven by BSA adsorption, flow cytometry and confocal microscopy assays. Results demonstrate that such type of polycations may serve as promising non-viral gene delivery vectors.

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“…[ 29,33 ] Briefl y, the HeLa/293T/ COS7 cells were fi rstly seeded in 96-well plates at a density of around 1.2 × 10 4 cells/well and cultured with 100 μ L of 10% FBS-containing DMEM for 24 h prior to adding the vehicle. After the vehicle was added for 48 h, the medium was replaced with 200 μ L of fresh medium.…”

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confidence: 99%

Theranostic GO‐Based Nanohybrid for Tumor Induced Imaging and Potential Combinational Tumor Therapy

Qin

Feng

Rong

et al. 2013

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Graphene oxide (GO)-based theranostic nanohybrid is designed for tumor induced imaging and potential combinational tumor therapy. The anti-tumor drug, Doxorubicin (DOX) is chemically conjugated to the poly(ethylenimine)-co-poly(ethylene glycol) (PEI-PEG) grafted GO via a MMP2-cleavable PLGLAG peptide linkage. The therapeutic efficacy of DOX is chemically locked and its intrinsic fluorescence is quenched by GO under normal physiological condition. Once stimulated by the MMP2 enzyme over-expressed in tumor tissues, the resulting peptide cleavage permits the unloading of DOX for tumor therapy and concurrent fluorescence recovery of DOX for in situ tumor cell imaging. Attractively, this PEI-bearing nanohybrid can mediate efficient DNA transfection and shows great potential for combinational drug/gene therapy. This tumor induced imaging and potential combinational therapy will open a window for tumor treatment by offering a unique theranostic approach through merging the diagnostic capability and pathology-responsive therapeutic function.

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A strategy to improve serum-tolerant transfection activity of polycation vectors by surface hydroxylation

Cited by 87 publications

References 53 publications

A Serum‐Tolerant Hydroxyl‐Modified Polyethylenimine as Versatile Carriers of pDNA/siRNA

A Serum‐Tolerant Hydroxyl‐Modified Polyethylenimine as Versatile Carriers of pDNA/siRNA

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

Theranostic GO‐Based Nanohybrid for Tumor Induced Imaging and Potential Combinational Tumor Therapy

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