A library of strictly linear poly(ethylene glycol)–poly(ethylene imine) diblock copolymers to perform structure–function relationship of non-viral gene carriers

Bauhuber, Sonja; Liebl, Renate; Tomasetti, Luise; Rachel, Reinhard; Goepferich, Achim; Breunig, Miriam

doi:10.1016/j.jconrel.2012.07.017

Cited by 39 publications

(24 citation statements)

References 37 publications

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“…24 h later, the polymer solution was precipitated in diethyl ether. The precipitate was washed three more times with diethyl ether and vacuum dried to obtain a yellow powder of poly(2‐ethyl‐2‐oxaline)‐bis(tosylate) (Ts‐PETOZ‐Ts) with a yield of 90% (8.9 g) . 1 H NMR (400 MHz, CDCl 3 , δ ): 7.71–7.69 (d, –C 6 H 4 CH 3 ), 7.16–7.14 (d, –C 6 H 4 CH 3 ), 3.46 (s, –CH 2 CH 2 NH–), 2.45–2.30 (m, –COCH 2 CH 3 and –C 6 H 4 CH 3 ), 1.21–1.11 (m, –COCH 2 CH 3 ) (Figure S2 in the Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

“…The resultant solution was dried with anhydrous magnesium sulfate. Finally, AcS‐PETOZ‐SAc was harvested by precipitation in cold diethyl ether (yield 90%, 4.4 g) . 1 H NMR (400 MHz, CDCl 3 , δ ): 3.46 (s, –CH 2 CH 2 NH–), 3.0–2.9 (t, –SCO–CH 3 ), 2.45–2.30 (m, –COCH 2 CH 3 ), 1.21–1.11 (m, –COCH 2 CH 3 ) (Figure S3 in the Supporting Information).…”

Section: Methodsmentioning

confidence: 99%

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Revisiting Complexation between DNA and Polyethylenimine: Does the Disulfide Linkage Play a Critical Role in Promoting Gene Delivery?

Chen

et al. 2014

Macromol. Biosci.

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Despite its cytotoxicity, polyethylenimine (PEI) is still used as a golden reference in gene transfection. Long PEI chains are more effective but also more cytotoxic. To solve this problem, an alternative strategy is to link short PEI chains into a longer PEI with disulfide bonds because they are degradable in the cell. However, how PEI promotes gene transfection is still unclear. Also, the chain length of PEI is also increased as disulfide bonds are formed. Therefore, it is important to investigate whether the increase in transfection efficiency is attributable to the disulfide linkage, chain size, or both. To distinguish between such factors, a novel method is developed here to make longer linear PEI with disulfide bonds (lPEI(s-s)) by linking the mercapto groups of short linear PEI (lPEI(i)). By comparing the physiochemical properties and the transfection efficiencies of short lPEI(i), long lPEI(s-s), and un-degradable long PEI, it is found that introducing disulfide bonds instead of directly using longer PEI chains has less effect on gene transfection, and it is the chain length that plays a key role in promoting gene transfection.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Revisiting Complexation between DNA and Polyethylenimine: Does the Disulfide Linkage Play a Critical Role in Promoting Gene Delivery?

Chen

et al. 2014

Macromol. Biosci.

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“…In order to overcome these drawbacks, PEI has been conjugated with poly(ethylene glycol) (PEG) to yield a range of block copolymer assemblies . Hyperbranched (hy)PEI‐ graft ‐PEG is one of the most studied polymeric gene carriers that produces sterically stabilized micelle nanoparticles with a PEI/DNA polyplex core and a brush corona layer of PEG on the surface.…”

Section: Introductionmentioning

confidence: 99%

“…The PEGylation of (hy)PEI is typically accomplished using chemical bonds which are relatively stable in the intracellular environment . The lack of biodegradability of (hy)PEI‐g‐PEG block copolymers prevents timely release of internalized DNA from the complex due to steric interferences of the still associated PEG chains . Furthermore, steric interference of PEG chains reduces PEI's ability to condense DNA into a compact polyplex particle, which coincidently reduces the polyplex micelles' stability in the presence of competing polyanions such as glycosaminoglycans .…”

Section: Introductionmentioning

confidence: 99%

Three‐Layered Biodegradable Micelles Prepared by Two‐Step Self‐Assembly of PLA‐PEI‐PLA and PLA‐PEG‐PLA Triblock Copolymers as Efficient Gene Delivery System

Abebe

Kandil

Kraus

et al. 2015

Macromolecular Bioscience

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"Three-layered micelles" (3LM) composed of two triblock copolymers, poly(L-lactide)-b-polyethyleneimine-b-poly(L-lactide) (PLLA-PEI-PLLA) and poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) are designed to combine electrostatic interaction and solvent-induced condensation of DNA. The low molecular weight PLLA-PEI-PLLA is synthesized by a facile amine-protection/deprotection approach and employed as a gene vector, compacting DNA as a polyplex core in the organo-micelles. The individual organo-micelle is further encapsulated within a PLLA-PEG-PLLA amphiphilic micelle leading to an aqueous stable colloidal dispersion. The resulting spherical 3LM possess a hydrodynamic diameter of ca. 200 nm and zeta potential close to neutral and display excellent stability to competing polyanions such as dextran sulfate in neutral pH (7.4). Such high stability is attributed to the complete shielding of the PEI/DNA polyplex core with an impermeable hydrophobic intermediate layer. However, greater than 90% of the encapsulated DNA are released within 30 min when exposed to slightly acidic pH (4.5). Based on our findings, a new class of non-viral delivery system for nucleic acids with superb stability and stealth properties is identified.

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“…Polymer molecular weight of conventional DNA delivery polymers such as linear PEI-PEG block copolymers has been shown to correlate positively with cytotoxicity. While increasing PEG chain length can reduce some of this toxicity, a PEG content higher than 50% was shown to also reduce transfection efficacy [100]. …”

Section: Cargo Unpacking/vector Degradation To Minimize Toxicitymentioning

confidence: 99%

Exploring the role of polymer structure on intracellular nucleic acid delivery via polymeric nanoparticles

Bishop

Kozielski

Green

2015

Journal of Controlled Release

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Intracellular nucleic acid delivery has the potential to treat many genetically-based diseases, however, gene delivery safety and efficacy remains a challenging obstacle. One promising approach is the use of polymers to form polymeric nanoparticles with nucleic acids that have led to exciting advances in non-viral gene delivery. Understanding the successes and failures of gene delivery polymers and structures is key to engineering optimal polymers for gene delivery in the future. This article discusses the polymer structural features that enable effective intracellular delivery of DNA and RNA, including protection of nucleic acid cargo, cellular uptake, endosomal escape, vector unpacking, and delivery to the intracellular site of activity. The chemical properties that aid in each step of intracellular nucleic acid delivery are described and specific structures of note are highlighted. Understanding the chemical design parameters of polymeric nucleic acid delivery nanoparticles is important to achieving the goal of safe and effective non-viral genetic nanomedicine.

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A library of strictly linear poly(ethylene glycol)–poly(ethylene imine) diblock copolymers to perform structure–function relationship of non-viral gene carriers

Cited by 39 publications

References 37 publications

Revisiting Complexation between DNA and Polyethylenimine: Does the Disulfide Linkage Play a Critical Role in Promoting Gene Delivery?

Revisiting Complexation between DNA and Polyethylenimine: Does the Disulfide Linkage Play a Critical Role in Promoting Gene Delivery?

Three‐Layered Biodegradable Micelles Prepared by Two‐Step Self‐Assembly of PLA‐PEI‐PLA and PLA‐PEG‐PLA Triblock Copolymers as Efficient Gene Delivery System

Exploring the role of polymer structure on intracellular nucleic acid delivery via polymeric nanoparticles

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