Low molecular weight polyethylenimines linked by β‐cyclodextrin for gene transfer into the nervous system

Tang, Guping; Guo, H. Y.; Alexis, Frank; Wang, X.; Zeng, Su; Lim, Teck Guan; Ding, Jeak Ling; Yang, Yi Yan; Wang, Shengjia

doi:10.1002/jgm.874

Cited by 164 publications

(117 citation statements)

References 30 publications

(33 reference statements)

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“…For example, this complex has an average particle size of approximately 200 nm and a zeta potential of approximately 40 mV. 16 PEI 600 -β-CyD also has an ideal transfection efficiency on numerous cancer cell lines. 25 This study showed that the cytotoxicity and apoptosis level of MSCs induced by PEI 600 -β-CyD are significantly lower than those induced by PEI25kDa, whereas the cytotoxicity and apoptosis levels induced by PEI 600 -β-CyD are slightly higher than those induced by PEI600Da.…”

Section: Discussionmentioning

confidence: 99%

“…PEI 600 -β-CyD was synthesized using the method described previously. 16 Briefly, β-CyD (0.42 g, 0.37 mmol) and 1,1-carbonyldiimidazole (CDI) (0.80 g, 5.2 mmol, #115533; Sigma-Aldrich) were dissolved in 6 mL N,N-dimethyl formamide (#D4551; Sigma-Aldrich). The mixture was stirred at room temperature for 1 hour under nitrogen and precipitated in cold diethyl ether (#296082; Sigma-Aldrich).…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

“…[13][14][15] We synthesized PEI 600 -β-CyD, a cationic polymer, in which PEI polymers with an MW of 600 Da are linked by β-CyD with low toxicity and high efficiency in neurons. 16 Bone morphogenetic proteins (BMPs) are vital growth factors in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) during osteogenesis and fracture repair. 17 Recombinant human BMP2 and BMP7 are clinically used in the revision of posterolateral spine fusion and long-bone nonunions.…”

Section: Introductionmentioning

confidence: 99%

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Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Tong¹,

Huang²,

Shi³

et al. 2013

IJN

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Genetically modified mesenchymal stem cells (MSCs) have great potential in the application of regenerative medicine and molecular therapy. In the present manuscript, we introduce a nanopolymer, polyethylenimine 600 -β-cyclodextrin (PEI 600 -β-CyD), as an efficient polyplex-forming plasmid delivery agent with low toxicity and ideal transfection efficiency on primary MSCs. PEI 600 -β-CyD causes significantly less cytotoxicity and apoptosis on MSCs than 25 kDa high-molecular-weight PEI (PEI25kDa). PEI 600 -β-CyD also exhibits similar transfection efficiency as PEI25kDa on MSCs, which is higher than that of PEI600Da. Quantum dot-labeled plasmids show that PEI 600 -β-CyD or PEI25kDa delivers the plasmids in a more scattered manner than PEI600Da does. Further study shows that PEI 600 -β-CyD and PEI25kDa are more capable of delivering plasmids into the cell lysosome and nucleus than PEI600Da, which correlates well with the results of their transfection-efficiency assay. Moreover, among the three vectors, PEI 600 -β-CyD has the most capacity of enhancing the alkaline phosphatase activity of MSCs by transfecting bone morphogenetic protein 2, 7, or special AT-rich sequence-binding protein 2. These results clearly indicate that PEI 600 -β-CyD is a safe and effective candidate for the nonviral gene delivery of MSCs because of its ideal inclusion ability and proton sponge effect, and the application of this nanopolymer warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Materials and Methods Materialsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Tong¹,

Huang²,

Shi³

et al. 2013

IJN

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“…19 The rapid DNA release in the reduction condition suggests that the significant polyplex dissociation was mainly owing to the cleavage of the amide bond with DTT, leading to increased DNA release and increased gene expression. 20 Degradation study and resistance to nuclease degradation Degradation of gene delivery polymers in vivo is important for safe and efficient gene delivery, because the appropriate degradation of the polymer could reduce cytotoxicity and facilitate elimination through the excretion pathway in vivo. 21,22 Nondegradable PEI may accumulate in vivo because of a lack of degradation or excretion pathways, causing potential cytotoxicity.…”

Section: Analysis and Characterization Of Polyplex Formationmentioning

confidence: 99%

Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

Fan

Wu²,

Ding

et al. 2012

IJN

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Background: Cationic copolymers consisting of polycations linked to nonionic amphiphilic block polymers have been evaluated as nonviral gene delivery systems, and a large number of different polymers and copolymers of linear, branched, and dendrimeric architectures have been tested in terms of their suitability and efficacy for in vitro and in vivo transfection. However, the discovery of new potent materials still largely relies on empiric approaches rather than a rational design. The authors investigated the relationship between the polymers' structures and their biological performance, including DNA compaction, toxicity, transfection efficiency, and the effect of cellular uptake. Methods: This article reports the synthesis and characterization of a series of cationic copolymers obtained by grafting polyethyleneimine with nonionic amphiphilic surfactant polyetherPluronic ® consisting of hydrophilic ethylene oxide and hydrophobic propylene oxide blocks.Transgene expression, cytotoxicity, localization of plasmids, and cellular uptake of these copolymers were evaluated following in vitro transfection of HeLa cell lines with various individual components of the copolymers. Results: Pluronics can exhibit biological activity including effects on enhancing DNA cellular uptake, nuclear translocation, and gene expression. The Pluronics with a higher hydrophiliclipophilic balance value lead to homogeneous distribution in the cytoplasm; those with a lower hydrophilic-lipophilic balance value prefer to localize in the nucleus. Conclusion:This Pluronic-polyethyleneimine system may be worth exploring as components in the cationic copolymers as the DNA or small interfering RNA/microRNA delivery system in the near future.

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“…This buffering protects the endocytosed gene from lysosomal degradation. [21][22][23][24][25] To reduce the cytotoxicity, hydrophilic molecules like polyethylene glycol (PEG) have been employed. PEG not only reduces toxicity but also prevents any unintended interaction of the encapsulated therapeutic molecule with cellular or serum proteins, thus enhancing stability of the polyplex and avoiding macrophage uptake.…”

Section: Introductionmentioning

confidence: 99%

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

Malhotra¹,

Tomaro-Duchesneau²,

Saha³

et al. 2013

IJN

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Recently, cell-penetrating peptides have been proposed to translocate antibodies, proteins, and other molecules in targeted drug delivery. The proposed study presents the synthesis and characterization of a peptide-based chitosan nanoparticle for small interfering RNA (siRNA) delivery, in-vitro. Specifically, the synthesis included polyethylene glycol (PEG), a hydrophilic polymer, and trans-activated transcription (TAT) peptide, which were chemically conjugated on the chitosan polymer. The conjugation was achieved using N-Hydroxysuccinimide-PEGmaleimide (heterobifunctional PEG) as a cross-linker, with the bifunctional PEG facilitating the amidation reaction through its N-Hydroxysuccinimide group and reacting with the amines on chitosan. At the other end of PEG, the maleimide group was chemically conjugated with the cysteine-modified TAT peptide. The degree of substitution on chitosan with PEG and on PEG with TAT was confirmed using colorimetric assays. The resultant polymer was used to form nanoparticles complexing siRNA, which were then characterized for particle size, morphology, cellular uptake, and cytotoxicity. The nanoparticles were tested in-vitro on mouse neuroblastoma cells (Neuro2a). Particle size and surface charge were characterized and an optimal pH condition and PEG molecular weight were determined to form sterically stable nanoparticles. Results indicate 7.5% of the amines in chitosan polymer were conjugated to the PEG and complete conjugation of TAT peptide was observed on the synthesized PEGylated chitosan polymer. Compared with unmodified chitosan nanoparticles, the nanoparticles formed at pH 6 were monodispersed and of ,100 nm in size, exhibiting maximum cell transfection ability and very low cytotoxicity. Thus, this research may be of significance in translocating biotherapeutic molecules for intracellular delivery applications.

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Low molecular weight polyethylenimines linked by β‐cyclodextrin for gene transfer into the nervous system

Cited by 164 publications

References 30 publications

Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

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Low molecular weight polyethylenimines linked by β‐cyclodextrin for gene transfer into the nervous system

Cited by 164 publications

References 30 publications

Polyethylenimine600-&beta;-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Polyethylenimine600-&beta;-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Degradable gene delivery systems based on Pluronics-modified low-molecular-weight polyethylenimine: preparation, characterization, intracellular trafficking, and cellular distribution

Development and characterization of chitosan-PEG-TAT nanoparticles for the intracellular delivery of siRNA

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Product

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Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells