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Anionic Chain-Growth Polymerization: Overview01:20

Anionic Chain-Growth Polymerization: Overview

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The polymerization process that involves carbanion as an intermediate is called anionic polymerization. It is also a type of addition or chain-growth polymerization. Anionic polymerization gets initiated by a strong nucleophile such as an organolithium or a Grignard reagent. The most commonly used initiator for anionic polymerization is butyl lithium. Monomers involved in anionic polymerization must possess a vinyl group bonded to one or two electron-withdrawing groups. For instance,...
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The cationic polymerization mechanism consists of three steps: initiation, propagation, and termination. In the initiation step of the polymerization process, the π bond of a monomer gets protonated by the Lewis acid catalyst, which is formed from boron trifluoride and water. The protonation of the π bond generates a carbocation stabilized by the electron‐donating group. In the propagation step, the π bond of the second monomer acts as a nucleophile and attacks the...
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Ion Exchange

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Ion exchange chromatography separates charged molecules from a solution by reversibly exchanging them with mobile, or 'active', ions associated with the oppositely charged stationary phase. This method can be used to separate ions, soften and deionize water, and purify solutions. The polymers comprising the ion-exchange column are high-molecular-weight and chemically stable polymers, crosslinked to be porous and essentially insoluble. They are also functionalized with either acidic or...
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Anionic Chain-Growth Polymerization: Mechanism01:04

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The mechanism for anionic chain-growth polymerization involves initiation, propagation, and termination steps. In the initiation step, a nucleophilic anion, such as butyl lithium, initiates the polymerization process by attacking the π bond of the vinylic monomer. As a result, a carbanion, stabilized by the electron‐withdrawing group, is generated. The resulting carbanion acts as a Michael donor in the propagation step and attacks the second vinylic monomer, which acts as a Michael...
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Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by &#960;-&#960; Stacking Interactions
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pH-sensitive packaging of cationic particles by an anionic block copolymer shell.

Jana I Solomun1, Liam Martin1, Prosper Mapfumo1

  • 1Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743, Jena, Germany.

Journal of Nanobiotechnology
|July 16, 2022
PubMed
Summary

Researchers developed a novel pH-responsive polymer shield to improve cationic non-viral vectors for gene delivery. This system enhances biocompatibility and transfection efficiency in various cells and shows promise for in vivo applications with reduced toxicity.

Keywords:
BiocompatibilityCharge maskingCore–shell nanoparticlesLayer-by-layerStealth polymers

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Area of Science:

  • Biomaterials Science
  • Gene Therapy
  • Polymer Chemistry

Background:

  • Cationic non-viral vectors are promising for gene delivery but face challenges with toxicity and systemic application.
  • Polyethylene glycol (PEG) shielding improves biocompatibility but often reduces transfection efficiency.
  • Developing effective, non-toxic gene delivery systems with enhanced cellular uptake and endosomal escape is crucial.

Purpose of the Study:

  • To design and evaluate a novel multicomponent polymer system for enhanced gene delivery.
  • To utilize a pH-responsive block copolymer as a shielding agent to improve biocompatibility and transfection efficiency.
  • To assess the performance, stability, and toxicity of the developed system in vitro and in vivo.

Main Methods:

  • Synthesis of cationic hydrophobic particles (PBMD) and a pH-responsive block copolymer (PNC) for shielding.
  • Characterization of PNC-shielded particles, including size, stability, and pDNA complexation.
  • Evaluation of in vitro transfection efficiency in adherent (HEK293T) and suspension (K-562) cells.
  • Assessment of cytotoxicity in human erythrocytes and K-562 cells.
  • Pilot in vivo study on mouse bone marrow blood cells.

Main Results:

  • PNC-shielded particles demonstrated stable pDNA complexation and remained below 200 nm in diameter.
  • The system showed pH-dependent behavior, preventing erythrocyte interaction at pH 7.4 but enabling membrane leakage at pH 6.
  • Transfection efficiency in HEK293T and K-562 cells was comparable or superior to commercial linear poly(ethylenimine) (LPEI).
  • Cytotoxicity was significantly reduced, particularly in K-562 cells and erythrocytes.
  • In vivo studies showed slightly enhanced cell transfection in mouse bone marrow cells compared to naked pDNA.

Conclusions:

  • The developed multicomponent polymer system, featuring pH-responsive shielding, offers a promising approach for efficient and safe gene delivery.
  • The pH-sensitive polymer (PNC) provides biocompatibility and stability while facilitating endosomal escape for high transfection rates.
  • This system overcomes limitations of traditional PEGylation, offering a viable alternative for both in vitro and in vivo gene transfection applications.