Construction of a 3-Miktoarm Star from Cyclic Polymers

Jia, Zhongfan; Lonsdale, Daria E.; Kulis, Jakov; Monteiro, Michael J.

doi:10.1021/mz300259v

Cited by 70 publications

(75 citation statements)

References 32 publications

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“…non-viral vectors), on the other hand, are relatively easy to synthesize, and are able to be designed with unique chemical composition and topology. [9][10][11][12][13][14][15] Although considerable research has been carried out for the use of polymers as delivery devices for pDNA, 16,17 there is a lack of understanding of how polymers enter the cells and deliver the pDNA into the nucleus. Due to the much larger size of the polymer/pDNA complexes (~50-200 nm) compared to the size of nuclear pores (~25 nm), it is believed that delivery of the complex is during cell division when the nuclear envelop is temporarily disintegrated.…”

Section: Introductionmentioning

confidence: 99%

Intracellular Trafficking Pathways for Nuclear Delivery of Plasmid DNA Complexed with Highly Efficient Endosome Escape Polymers

et al. 2014

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Understanding the pathways for nuclear entry could see vast improvements in polymer design for the delivery of genetic materials to cells. Here, we use a novel diblock copolymer complexed with plasmid DNA (pDNA) to determine both its cellular entry and nuclear pathways. The diblock copolymer (A-C3) is specifically designed to bind and protect pDNA, release it at a specific time, but more importantly, rapidly escape the endosome. The copolymer was taken up by HEK293 cells preferentially via the clathrin-mediated endocytosis (CME) pathway, and the pDNA entered the nucleus to produce high gene expression levels in all cells after 48 h, a similar observation to the commercially available polymer transfection agent, PEI Max. This demonstrates that the polymers must first escape the endosome and then mediate transport of pDNA to the nucleus for occurrence of gene expression. The amount of pDNA within the nucleus was found to be higher for our A-C3 polymer than PEI Max, with our polymer delivering 7 times more pDNA than PEI Max after 24 h. We further found that entry into the nucleus was primarily through the small nuclear pores and did not occur during mitosis when the nuclear envelope becomes compromised. The observation that the polymers are also found in the nucleus supports the hypothesis that the large pDNA/polymer complex (size ~200 nm) must dissociate prior to nucleus entry and that cationic and hydrophobic monomer units on the polymer may facilitate active transport of the pDNA through the nuclear pore.

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Section: Introductionmentioning

confidence: 99%

Intracellular Trafficking Pathways for Nuclear Delivery of Plasmid DNA Complexed with Highly Efficient Endosome Escape Polymers

et al. 2014

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“…Living radical polymerization (LRP)30–34 (also termed reversible deactivation radical polymerization) is a robust and versatile tool to synthesize well‐defined polymers and has been utilized in the synthesis of ABC‐type miktoarm stars. Different LRP techniques such as nitroxide‐mediated radical polymerization, atom transfer radical polymerization, and reversible addition‐fragmentation chain transfer polymerization, were combined to synthesize stars bearing three different arms through the “coupling‐onto” and “combinatorial” approaches 35,36. The synthesis of ABC miktoarm stars using a single LRP technique was achieved through “combinatorial” approach37 but is still rare.…”

Section: Synthesis Of Abc Miktoarm Star Copolymersmentioning

confidence: 99%

Synthesis of ABC Miktoarm Star Copolymers via Organocatalyzed Living Radical Polymerization

Chen

Sim

et al. 2020

Macromol. Rapid Commun.

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ABC‐type miktoarm star copolymers are synthesized using a single living radical polymerization (organocatalyzed living radical polymerization) via a “combinatorial” approach. The arm A is poly(butyl acrylate), the arm B is poly(methyl methacrylate), and the arm C encompasses hydrophobic and hydrophilic polyacrylates. A poly(butyl acrylate) with a vinyl chain end (macromonomer) is synthesized. A poly(methyl methacrylate) is subsequently connected to the reactive vinyl group to generate diblock copolymer. From the junction of the diblock copolymer, polymer C grew to yield star copolymers. An amphiphilic star copolymer is also synthesized, and its self‐assembly structure is studied in an aqueous solution.

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“…Lutz et al employed ATRP to prepare a range of linear PS with alkyne and/or azide functional groups installed at various positions along the polymers [171,172]. Monteiro et al employed ring polymers prepared from click ring closure as cyclic macromonomers and successfully constructed a diverse range of topological polymers, which include tadpole-shaped (i), double-ring (vi) and triple-ring polymers (x) through a second click coupling [199,200]. The subsequent intramolecular click coupling or Glaser coupling was performed under ultra-dilution to afford an array of folded polymer architectures with tadpole (i), alpha (ii) and figure-of-eight shape (vi) [172].…”

Section: Advanced Cyclic Polymer Constructsmentioning

confidence: 99%

Synthetic Strategies towards Well‐Defined Complex Polymeric Architectures through Covalent Chemistry

Ren

Qiao

2014

Chemie Ingenieur Technik

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Macromolecular architecture is a key factor determining the materials properties of polymers. Exploration of novel structural arrangements has become a viable means to develop advanced functional nanomaterials. Recent developments in polymer chemistry have forged robust synthetic platforms for innovative polymeric materials with highly regulated structures, functionalities, and compositions. This review summarizes the latest synthetic strategies for well-defined polymer architectures through covalent chemistry, with the focus on four main types of well-defined macromolecular constructs.

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Construction of a 3-Miktoarm Star from Cyclic Polymers

Cited by 70 publications

References 32 publications

Intracellular Trafficking Pathways for Nuclear Delivery of Plasmid DNA Complexed with Highly Efficient Endosome Escape Polymers

Intracellular Trafficking Pathways for Nuclear Delivery of Plasmid DNA Complexed with Highly Efficient Endosome Escape Polymers

Synthesis of ABC Miktoarm Star Copolymers via Organocatalyzed Living Radical Polymerization

Synthetic Strategies towards Well‐Defined Complex Polymeric Architectures through Covalent Chemistry

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