Hyperbranched poly(ethylenimine-<i>co</i>-oxazoline) by thiol–yne chemistry for non-viral gene delivery: investigating the role of polymer architecture

Cook, Alexander; Peltier, Raoul; Zhang, Junliang; Gurnani, Pratik; Tanaka, Joji; Burns, James R.; Dallmann, Robert; Hartlieb, Matthias; Perrier, Sébastien

doi:10.1039/c8py01648h

Cited by 47 publications

(48 citation statements)

References 58 publications

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“…185,186 In a recent study, we reported the synthesis of hyperbranched poly(ethyleneimine-co-oxazoline) by combination of thiol-yne photoaddition chemistry with well-defined linear ethyleneimine-co-oxazoline copolymers (Figure 7). 126 This new PEI hyperbranched architecture with only secondary amines (compared to bPEI with primary, secondary, and tertiary amines) was used to complex and deliver plasmid DNA coding for GFP. In vitro toxicity assays and gene transfection experiments with HEK293T cell-line, highlighted the impact of polymer architecture, as the hyperbranched structure showed lower toxicity but similar transfection efficiencies compared to the equivalent linear p(ethyleneimineco-oxazoline) copolymers.…”

Section: Long Chain Hyperbranched Polymersmentioning

confidence: 99%

“…a) Hyperbranched p(ethyleneimine-co-oxazoline), with varying ethyleneimine contents from 32% to 78%, by thiol-yne chemistry for use in the delivery of plasmid DNA with a GFP reporter gene, b) polymer toxicity as determined by XTT assay in HEK293T cells, c) proportion GFP positive cells and mean fluorescent intensities of transfected HEK293T cells compared to commercial branched PEI. Figure adapted with permission126 . Copyright 2019 Royal Society of Chemistry.…”

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confidence: 99%

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Branched and Dendritic Polymer Architectures: Functional Nanomaterials for Therapeutic Delivery

Cook

Perrier

2019

Adv Funct Materials

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128

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Barriers to therapeutic transport in biological systems can prevent accumulation of drugs at the intended site, thus limiting the therapeutic effect against various diseases. Advances in synthetic chemistry techniques have recently increased the accessibility of complex polymer architectures for drug delivery systems, including branched polymer architectures. This article first outlines drug delivery concepts, and then defines and illustrates all forms of branched polymers including highly branched polymers, hyperbranched polymers, dendrimers, and branched–linear hybrid polymers. Many new types of branched and dendritic polymers continue to be reported; however, there is often confusion about how to accurately describe these complex polymer architectures, particularly in the interdisciplinary field of nanomedicine where not all researchers have in‐depth polymer chemistry backgrounds. In this context, the present review describes and compares different branched polymer architectures and their application in therapeutic delivery in a simple and easy‐to‐understand way, with the aim of appealing to a multidisciplinary audience.

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Section: Long Chain Hyperbranched Polymersmentioning

confidence: 99%

mentioning

confidence: 99%

Branched and Dendritic Polymer Architectures: Functional Nanomaterials for Therapeutic Delivery

Cook

Perrier

2019

Adv Funct Materials

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128

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“…Like dendrimers, HBPs form cavities that can be used to encapsulate cargos of different sizes [118] including small chemotherapeutic drugs such as DOX, [119,120] camptothecin (CPT), [121,122] cisplatin, [123][124][125] [127][128][129][130] and siRNA [131][132][133] form complexes with unimolecular HBPs such as branched poly(ethylene imine) (PEI) [134] by electrostatic interactions. Tuning the structure of HBPs permits to control the strength of the interaction between gene and carrier by modulating the charge density at its surface, adjusting its molecular weight, and preparing different molecular structures.…”

Section: Drug Loadingmentioning

confidence: 99%

Synthesis and functionalization of hyperbranched polymers for targeted drug delivery

Kavand

Anton

Vandamme

et al. 2020

Journal of Controlled Release

108

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Hyperbranched polymers (HBPs) have found use in a wide range of applications, such as optical, electronic and magnetic materials, coatings, additives, supramolecular chemistry, and biomedicine. HBPs have gained attention for the development of drug delivery systems due to the presence of internal cavities in their three-dimensional globular structure that can be used to encapsulate drugs and their facile synthesis as compared to dendrimers. The composition, topology, and functionality of HBPs have been tuned to design drug carriers with better efficacies. Recent advances have been reported to introduce functional groups to enhance targeting tumor cells. HBPs have been modified to promote passive and active targeting. This review article will describe the different routes to synthesize hyperbranched polymer, their use as drug carriers for targeted drug delivery, and their functionalization with ligands for active targeting through various synthesis strategies to give the reader an extended overview of the progresses accomplished in this field. The modification of HBPs with ligands such as peptides, oligonucleotides, and folic acid have been demonstrated to enhance the accumulation of the drug selectively at the tumor sites. The potential uses and developments of HBPs as nanoobjects for theranostics for example are discussed as perspectives.

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“…Polyethylenimine (PEI) is the most studied cationic polymer for gene delivery, and branched PEI 25 kDa has been considered as the golden standard for new polymeric non-viral vectors on account of its high transfection efficiency (TE), which is attributed to the strong buffering capacity in the pH range of 7.4-5.1 [9]. Although high molecular weight PEI shows good TE, it also exhibits obvious cytotoxicity for its non-degradable and highly positively charged structure [10,11]. Reducing molecular weight could solve the toxicity problem, but the TE is sacrificed [12].…”

Section: Introductionmentioning

confidence: 99%

Amino Acid-Linked Low Molecular Weight Polyethylenimine for Improved Gene Delivery and Biocompatibility

Zhang

et al. 2020

Molecules

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The construction of efficient and low toxic non-viral gene delivery vectors is of great significance for gene therapy. Herein, two novel polycations were constructed via Michael addition from low molecular weight polyethylenimine (PEI) 600 Da and amino acid-containing linkages. Lysine and histidine were introduced for the purpose of improved DNA binding and pH buffering capacity, respectively. The ester bonds afforded the polymer biodegradability, which was confirmed by the gel permeation chromatography (GPC) measurement. The polymers could well condense DNA into nanoparticles and protect DNA from degradation by nuclease. Compared with PEI 25 kDa, these polymers showed higher transfection efficiency, lower toxicity, and better serum tolerance. Study of this mechanism revealed that the polyplexes enter the cells mainly through caveolae-mediated endocytosis pathway; this, together with their biodegradability, facilitates the internalization of polyplexes and the release of DNA. The results reveal that the amino acid-linked low molecular weight PEI polymers could serve as promising candidates for non-viral gene delivery.

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Hyperbranched poly(ethylenimine-co-oxazoline) by thiol–yne chemistry for non-viral gene delivery: investigating the role of polymer architecture

Abstract: Synthesis of long-chain hyperbranched poly(ethylenimine-co-oxazoline)s by AB2 thiol–yne chemistry is reported, and their application as pDNA transfection agents studied.

Cited by 47 publications

References 58 publications

Branched and Dendritic Polymer Architectures: Functional Nanomaterials for Therapeutic Delivery

Branched and Dendritic Polymer Architectures: Functional Nanomaterials for Therapeutic Delivery

Synthesis and functionalization of hyperbranched polymers for targeted drug delivery

Amino Acid-Linked Low Molecular Weight Polyethylenimine for Improved Gene Delivery and Biocompatibility

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