Low molecular weight PEI-based polycationic gene vectors via Michael addition polymerization with improved serum-tolerance

Xun, Miao-Miao; Xiao, Yaping; Zhang, Ji; Liu, Yanhong; Pan, Qi; Guo, Qin; Wu, Wan‐Xia; Xu, Yongjian; Yu, Xiao‐Qi

doi:10.1016/j.polymer.2015.03.070

Cited by 29 publications

(33 citation statements)

References 40 publications

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Section: Synthesis and Characterization Of Acylated Polymersmentioning

confidence: 82%

“…On the contrary, after condensation with the polymers, DNA could resist DNase and be released by subsequent addition of heparin. Such results suggest that these polymers may well protect DNA from degradation in the circumstance with nuclease [21]. Since cells typically take up particles ranging from micrometers to nanometers [22], it is necessary for the cationic polymers to compact nucleic acids into nanoparticles with proper zeta potentials, which also play an important role in endocytosis and material cytotoxicity [23].…”

Section: Formation Of Polymer/dna Complexes (Polyplexes)mentioning

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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Section: Synthesis and Characterization Of Acylated Polymersmentioning

confidence: 82%

Section: Formation Of Polymer/dna Complexes (Polyplexes)mentioning

confidence: 99%

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

et al. 2015

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“…We also investigated decomplexation of polyplexes by heparin, which is more negatively charged than DNA, and can lead to DNA release by its stronger interaction with cationic polymers. [ 9,33,34 ] As shown in Figure 5 B, DNA is gradually released with increasing concentration of heparin, and the threshold amounts of heparin at which polyplex dissociation occurred were 0.9, 0.6, and 0.2 IU (International Unit) for POEI 1, 2, and 3, respectively, suggesting that polyplexes formed with POEIs bearing more primary/secondary amines have higher DNA binding ability. In addition, DNase I is extremely dangerous for exogenous gene during the movement of DNA through cytosol toward the nucleus.…”

Section: Formation and Stability Of Poeis/dna Polyplexesmentioning

confidence: 88%

“…[ 9,[37][38][39] Promising polycationic gene vectors should have high gene transfection capability Early View Publication; these are NOT the final page numbers, use DOI for citation !! as well as low cytotoxicity.…”

Section: Cytotoxicity and In Vitro Gene Transfectionmentioning

confidence: 99%

“…[ 2,6,7 ] Among them, PEI has been widely used for nonviral transfection in vivo and in vitro because of its strong DNA condensation ability and efficient escape from endocytic pathway through "proton sponge" mechanism. [ 8,9 ] Studies indicate that gene transfection effi ciency and cytotoxicity of PEI correlated with their molecular weight and topology. High molecular weight PEI (HMW PEI) can form tight complexes with nucleic acids and protect DNA cargoes from degradation by lysosomal enzymes, but exhibits pronounced cytotoxicity due to cell membrane disruption followed by induction of apoptosis via destabilization of mitochondrial membranes.…”

Section: Introductionmentioning

confidence: 99%

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Low Molecular Weight PEI‐Based Vectors via Acid‐Labile Ortho Ester Linkage for Improved Gene Delivery

Zhang

Wang

et al. 2016

Macromolecular Bioscience

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A series of novel pH-sensitive gene delivery vectors (POEI 1, 2, and 3) are synthesized through Michael addition from low molecular weight PEI (LMW PEI) via acid-labile ortho ester linkage with terminal acrylates (OEAc) by various feed molar ratios. The obtained POEI 1 and POEI 2 can efficiently condense plasmid DNA into nanoparticles with size range of 200-300 nm and zeta-potentials of about +15 mV while protecting DNA from enzymatic digestion compared with POEI 3. Significantly, ortho ester groups of POEI main-chains can make an instantaneous degradation-response to acidic endosomal pH (≈5.0), resulting in accelerated disruption of polyplexes and intracellular DNA release. MTT assay reveals that all POEIs exhibit much lower cytotoxicity in different cells than branched PEI (25 KDa). As expected, POEI 1 and POEI 2 perform improved gene transfection in vitro, suggesting that such polycations might be promising gene vectors based on overcoming toxicity-efficiency contradiction.

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Rotational barriers of carbamate‐protected amine crosslinkers for hydrogels: A combined experimental and computational study

Schädel

Gebhardt

Löffler

et al. 2019

J of Physical Organic Chem

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Diethylenetriamines and diethanolamines carrying a carbamate‐protected amine and peripheral reactive units are valuable synthetic building blocks for hydrogel crosslinkers or biohybrid materials because they enable orthogonal functionalization. However, the carbamate unit leads to restricted rotational mobility, affecting both physical and chemical properties of the amines. To gain insight into the rotational behavior of such systems, a series of carbamate‐protected amines with different peripheral units was synthesized and their rotational barriers were studied by dynamic NMR measurements and electronic structure calculations. Experimentally observed barriers were in the range of 61 to 66 kJ/mol and were mostly dependent on the size of the peripheral groups rather than their hydrogen bonding ability. Density functional theory (DFT) and MP2 calculations yielded barriers of similar order of magnitude, albeit differing in the overall trends. The data suggest that for improved theoretical estimates of free energy barriers ab initio molecular dynamics simulations in explicit solvent would be required.

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Low molecular weight PEI-based polycationic gene vectors via Michael addition polymerization with improved serum-tolerance

Cited by 29 publications

References 40 publications

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

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

Low Molecular Weight PEI‐Based Vectors via Acid‐Labile Ortho Ester Linkage for Improved Gene Delivery

Rotational barriers of carbamate‐protected amine crosslinkers for hydrogels: A combined experimental and computational study

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