3rd generation poly(ethylene imine)s for gene delivery

Buś, Tanja; Englert, Christoph; Reifarth, Martin; Borchers, Philipp; Hartlieb, Matthias; Vollrath, Antje; Hoeppener, Stephanie; Traeger, Anja; Schubert, Ulrich S.

doi:10.1039/c6tb02592g

Cited by 42 publications

(53 citation statements)

References 56 publications

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“…P1 exhibits a concentration‐dependent cytotoxicity in the cell lines observed using the AlamarBlue assay (Figure ). Increased concentrations result in reduced cell viability, as reported before for LPEI of the respective molecular mass . Treatment with 5 μg mL −1 decreases the cell viability to 15.8% in L929 cells, 2.8% in HUVEC and 1% in MDA‐MB‐231 cells, respectively.…”

Section: Resultssupporting

confidence: 75%

“…The efficient delivery of nucleic acids into cells comes along with several requirements. Among others, this comprises the condensation of genetic material in a compact mode as well as the dissociation from the vector after it has been transferred into the cellular cytoplasm or nucleus …”

Section: Resultsmentioning

confidence: 99%

“…Even if the transfection investigations for P3 failed, the described modification of cationic polymers can be used to further develop the concept of d ‐fructose conjugated cationic polymers. Potential approaches for future research to increase the transfection efficiencies are the synthesis of different polymer compositions varying the ethylene imine/sugar ratio and, additionally, the introduction of amino functionalities to the side chains (analog to Ref …”

Section: Resultsmentioning

confidence: 99%

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d‐Fructose‐Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting

Englert

Pröhl

Czaplewska

et al. 2017

Macromolecular Bioscience

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The high affinity of GLUT5 transporter for d-fructose in breast cancer cells has been discussed intensely. In this contribution, high molar mass linear poly(ethylene imine) (LPEI) is functionalized with d-fructose moieties to combine the selectivity for the GLUT5 transporter with the delivery potential of PEI for genetic material. The four-step synthesis of a thiol-group bearing d-fructose enables the decoration of a cationic polymer backbone with d-fructose via thiol-ene photoaddition. The functionalization of LPEI is confirmed by 2D NMR techniques, elemental analysis, and size exclusion chromatography. Importantly, a d-fructose decoration of 16% renders the polymers water-soluble and eliminates the cytotoxicity of PEI in noncancer L929 cells, accompanied by a reduced unspecific cellular uptake of the genetic material. In contrast, the cytotoxicity as well as the cell specific uptake is increased for triple negative MDA-MB-231 breast cancer cells. Therefore, the introduction of d-fructose shows superior potential for cell targeting, which can be assumed to be GLUT5 dependent.

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Section: Resultssupporting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

d‐Fructose‐Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting

Englert

Pröhl

Czaplewska

et al. 2017

Macromolecular Bioscience

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“…The introduction of the microwave technique in 2004 reduced the reaction times from several days to minutes, by keeping the controlled character of the CROP and resulting in well‐defined polymers . The application of functional initiators or terminating agents results in α‐ and ω‐functionalized P(Ox)s . Furthermore, 2‐oxazolines can be easily modified in the 2‐position, leading to a high chemical versatility for structural modification through copolymerization.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, 2‐oxazolines can be easily modified in the 2‐position, leading to a high chemical versatility for structural modification through copolymerization. The utilization of the hydrophilic monomers MeOx and EtOx results in water‐soluble polymers, which also mediate stealth behavior and facilitate the reduction of cytotoxicity . In 2015, our group showed advantages of amino functionalized P(Ox)s toward l ‐PEI, by using a library approach .…”

Section: Introductionmentioning

confidence: 99%

Comparison of random and gradient amino functionalized poly(2‐oxazoline)s: Can the transfection efficiency be tuned by the macromolecular structure?

Hertz

Leiske

Wloka

et al. 2018

J. Polym. Sci. Part A: Polym. Chem.

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Poly(ethylene imine) can be considered as the gold standard for DNA delivery into cells in vitro, but severe cytotoxic side‐effects and inapplicability for targeted approaches in vivo urgently call for the design of new gene carriers. Since poly(2‐oxazoline)s (P(Ox)s) can be easily synthesized and modified, this polymer class might be ideal for the optimization of polymeric transfection processes. The utilization of 2‐methyl‐2‐oxazoline (MeOx) and 2‐ethyl‐2‐oxazoline (EtOx) is also known to be beneficial because these monomers were suggested to overcome solubility issues, mediate stealth behavior and, consequently, facilitate a reduction of cytotoxicity. A series of amino (AmOx) functionalized P(Ox) copolymers with either MeOx (gradient copolymers) or EtOx (random copolymers) was synthesized, deprotected and biochemically characterized regarding cytotoxicity, polyplex formation ability, cellular uptake, and transfection efficiency. Polymers with percentages of AmOx higher than 35 mol % showed stable polyplex formation and also an increase in cytotoxicity. All elucidated P(Ox)s revealed a poor transfection efficiency in both L929 and Hepa1‐6 cell lines. However, the investigations contribute to the understanding of the influence of stealth units (MeOx and EtOx) and their distribution within the polymer chain on selected properties of polyplexes and describe characteristics of amino functionalized P(Ox)s in different cell lines. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1210–1224

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Uptake and Intracellular Fate of Engineered Nanoparticles in Mammalian Cells: Capabilities and Limitations of Transmission Electron Microscopy—Polymer‐Based Nanoparticles

2018

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In order to elucidate mechanisms of nanoparticle (NP)-cell interactions, a detailed knowledge about membrane-particle interactions, intracellular distributions, and nucleus penetration capabilities, etc. becomes indispensable. The utilization of NPs as additives in many consumer products, as well as the increasing interest of tailor-made nanoobjects as novel therapeutic and diagnostic platforms, makes it essential to gain deeper insights about their biological effects. Transmission electron microscopy (TEM) represents an outstanding method to study the uptake and intracellular fate of NPs, since this technique provides a resolution far better than the particle size. Additionally, its capability to highlight ultrastructural details of the cellular interior as well as membrane features is unmatched by other approaches. Here, a summary is provided on studies utilizing TEM to investigate the uptake and mode-of-action of tailor-made polymer nanoparticles in mammalian cells. For this purpose, the capabilities as well as limitations of TEM investigations are discussed to provide a detailed overview on uptake studies of common nanoparticle systems supported by TEM investigations. Furthermore, methodologies that can, in particular, address low-contrast materials in electron microscopy, i.e., polymeric and polymer-modified nanoparticles, are highlighted.

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3rd generation poly(ethylene imine)s for gene delivery

Abstract: In this study, a series of high molar mass poly(2-oxazoline)-based copolymers was synthesized, introducing 2-ethyl-2-oxazoline, ethylene imine, and primary amine bearing monomer units representing a new generation of PEI.

Cited by 42 publications

References 56 publications

d‐Fructose‐Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting

d‐Fructose‐Decorated Poly(ethylene imine) for Human Breast Cancer Cell Targeting

Comparison of random and gradient amino functionalized poly(2‐oxazoline)s: Can the transfection efficiency be tuned by the macromolecular structure?

Uptake and Intracellular Fate of Engineered Nanoparticles in Mammalian Cells: Capabilities and Limitations of Transmission Electron Microscopy—Polymer‐Based Nanoparticles

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