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Title: Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic—Neutral Hydrophilic Block Copolymers

Abstract

Polyelectrolyte complex micelles (PCMs, core-shell nanoparticles formed by complexation of a polyelectrolyte with a polyelectrolyte-hydrophilic neutral block copolymer) offer a solution to the critical problem of delivering therapeutic nucleic acids, Despite this, few systematic studies have been conducted on how parameters such as polycation charge density, hydrophobicity, and choice of charged group influence PCM properties, despite evidence that these strongly influence the complexation behavior of polyelectrolyte homopolymers. In this article, we report a comparison of oligonucleotide PCMs and polyelectrolyte complexes formed by poly(lysine) and poly((vinylbenzyl) trimethylammonium) (PVBTMA), a styrenic polycation with comparatively higher charge density, increased hydrophobicity, and a permanent positive charge. All of these differences have been individually suggested to provide increased complex stability, but we find that PVBTMA in fact complexes oligonucleotides more weakly than does poly(lysine), as measured by stability versus added salt. Using small angle X-ray scattering and electron microscopy, we find that PCMs formed from both cationic blocks exhibit very similar structure-property relationships, with PCM radius determined by the cationic block size and shape controlled by the hybridization state of the oligonucleotides. These observations narrow the design space for optimizing therapeutic PCMs and provide new insights into the rich polymer physics of polyelectrolyte self-assembly.

Authors:
 [1];  [1];  [2];  [3];  [2]
  1. Univ. of Chicago, IL (United States)
  2. Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Lemont, IL (United States)
  3. Swarthmore College, PA (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Materials Sciences & Engineering Division; National Institute of Standards and Technology (NIST) - Center for Hierarchical Materials Design (CHiMaD)
OSTI Identifier:
1494914
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Polymers
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 2073-4360
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; complex coacervation; nanoparticles; oligonucleotides; phase separation; polyelectrolytes

Citation Formats

Marras, Alexander E., Vieregg, Jeffrey R., Ting, Jeffrey M., Rubien, Jack D., and Tirrell, Matthew V. Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic—Neutral Hydrophilic Block Copolymers. United States: N. p., 2019. Web. doi:10.3390/polym11010083.
Marras, Alexander E., Vieregg, Jeffrey R., Ting, Jeffrey M., Rubien, Jack D., & Tirrell, Matthew V. Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic—Neutral Hydrophilic Block Copolymers. United States. doi:10.3390/polym11010083.
Marras, Alexander E., Vieregg, Jeffrey R., Ting, Jeffrey M., Rubien, Jack D., and Tirrell, Matthew V. Mon . "Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic—Neutral Hydrophilic Block Copolymers". United States. doi:10.3390/polym11010083. https://www.osti.gov/servlets/purl/1494914.
@article{osti_1494914,
title = {Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic—Neutral Hydrophilic Block Copolymers},
author = {Marras, Alexander E. and Vieregg, Jeffrey R. and Ting, Jeffrey M. and Rubien, Jack D. and Tirrell, Matthew V.},
abstractNote = {Polyelectrolyte complex micelles (PCMs, core-shell nanoparticles formed by complexation of a polyelectrolyte with a polyelectrolyte-hydrophilic neutral block copolymer) offer a solution to the critical problem of delivering therapeutic nucleic acids, Despite this, few systematic studies have been conducted on how parameters such as polycation charge density, hydrophobicity, and choice of charged group influence PCM properties, despite evidence that these strongly influence the complexation behavior of polyelectrolyte homopolymers. In this article, we report a comparison of oligonucleotide PCMs and polyelectrolyte complexes formed by poly(lysine) and poly((vinylbenzyl) trimethylammonium) (PVBTMA), a styrenic polycation with comparatively higher charge density, increased hydrophobicity, and a permanent positive charge. All of these differences have been individually suggested to provide increased complex stability, but we find that PVBTMA in fact complexes oligonucleotides more weakly than does poly(lysine), as measured by stability versus added salt. Using small angle X-ray scattering and electron microscopy, we find that PCMs formed from both cationic blocks exhibit very similar structure-property relationships, with PCM radius determined by the cationic block size and shape controlled by the hybridization state of the oligonucleotides. These observations narrow the design space for optimizing therapeutic PCMs and provide new insights into the rich polymer physics of polyelectrolyte self-assembly.},
doi = {10.3390/polym11010083},
journal = {Polymers},
issn = {2073-4360},
number = 1,
volume = 11,
place = {United States},
year = {2019},
month = {1}
}

Journal Article:
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Figures / Tables:

Figure 1 Figure 1: Polyelectrolyte complexation and PCM nanoparticle formation. DNA is a highly charged polyanion. When mixed with polycations (right), polyelectrolyte complexes are formed (macrophase separation). When mixed with cation-hydrophilic neutral block copolymers (left), microphase separation produces PCMs. In both scenarios, the hybridization state of the nucleic acid (singlevs. double-stranded) determinesmore » the nature of the product (liquid droplets vs. solid precipitates for the complexes, spheroidal vs. cylindrical PCMs). This study compares the effect of hydrophilic (poly(lysine), PLys) and hydrophobic (poly((vinylbenzyl) trimethylammonium), PVBTMA) polycations in determining the properties of the complexes and PCMs.« less

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