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

Marras, Alexander E.; Vieregg, Jeffrey R.; Ting, Jeffrey M.; Rubien, Jack D.; Tirrell, Matthew V.

doi:10.3390/polym11010083

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

Journal Article · 07 January 2019 · Polymers

DOI: https://doi.org/10.3390/polym11010083 · OSTI ID:1494914

Marras, Alexander E. ^[1]; Vieregg, Jeffrey R. ^[1]; Ting, Jeffrey M. ^[2]; Rubien, Jack D. ^[3]; Tirrell, Matthew V. ^[2]

Univ. of Chicago, IL (United States)
Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Lemont, IL (United States)
Swarthmore College, PA (United States)

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: 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)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1494914

Journal Information:: Polymers, Vol. 11, Issue 1; ISSN 2073-4360

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 32 works

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pH and Salt Effects on the Associative Phase Separation of Oppositely Charged Polyelectrolytes Jha, Prateek; Desai, Priyanka; Li, Jingyi Polymers, Vol. 6, Issue 5 https://doi.org/10.3390/polym6051414	journal	May 2014
The Effect of Salt on the Complex Coacervation of Vinyl Polyelectrolytes Perry, Sarah; Li, Yue; Priftis, Dimitrios Polymers, Vol. 6, Issue 6 https://doi.org/10.3390/polym6061756	journal	June 2014

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
complex coacervation
nanoparticles
oligonucleotides
phase separation
polyelectrolytes