Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles
Abstract
A series of model polyelectrolyte complex micelles (PCMs) was prepared to investigate the consequences of neutral and zwitterionic chemistries and distinct charged cores on the size and stability of nanocarriers. Using aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization, we synthesized a well-defined diblock polyelectrolyte system, poly(2-methacryloyloxyethyl phosphorylcholine methacrylate)-block-poly((vinylbenzyl) trimethylammonium) (PMPC-PVBTMA), at various neutral and charged block lengths to compare directly against PCM structure–property relationships centered on poly(ethylene glycol)-block-poly((vinylbenzyl) trimethylammonium) (PEG-PVBTMA) and poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLK). After complexation with a common polyanion, poly(sodium acrylate), the resulting PCMs were characterized by dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). We observed uniform assemblies of spherical micelles with a diameter ~1.5–2× larger when PMPC-PVBTMA was used compared to PEG-PLK and PEG-PVBTMA via SAXS and DLS. In addition, PEG-PLK PCMs proved most resistant to dissolution by both monovalent and divalent salt, followed by PEG-PVBTMA then PMPC-PVBTMA. All micelle systems were serum stable in 100% fetal bovine serum over the course of 8 h by time-resolved DLS, demonstrating minimal interactions with serum proteins and potential as in vivo drug delivery vehicles. This thorough study of the synthesis, assembly, and characterization of zwitterionic polymers in PCMs advances the design space for charge-driven micelle assemblies.
- Authors:
-
[1];
[2];
- Univ. of Chicago, IL (United States). Pritzker School of Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States). Materials Science Division. Center for Molecular Engineering
- Univ. of Chicago, IL (United States). Pritzker School of Molecular Engineering; Argonne National Lab. (ANL), Argonne, IL (United States). Materials Science Division. Center for Molecular Engineering
- Univ. of Chicago, IL (United States). Pritzker School of Molecular Engineering
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1815837
- Grant/Contract Number:
- AC02-06CH11357; AC02-76SF00515
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Molecules
- Additional Journal Information:
- Journal Volume: 25; Journal Issue: 11; Journal ID: ISSN 1420-3049
- Publisher:
- MDPI
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; polyelectrolyte complexes; micelles; zwitterions; PEG; polymer chemistry
Citation Formats
Ting, Jeffrey M., Marras, Alexander E., Mitchell, Joseph D., Campagna, Trinity R., and Tirrell, Matthew V. Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles. United States: N. p., 2020.
Web. doi:10.3390/molecules25112553.
Ting, Jeffrey M., Marras, Alexander E., Mitchell, Joseph D., Campagna, Trinity R., & Tirrell, Matthew V. Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles. United States. https://doi.org/10.3390/molecules25112553
Ting, Jeffrey M., Marras, Alexander E., Mitchell, Joseph D., Campagna, Trinity R., and Tirrell, Matthew V. Sat .
"Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles". United States. https://doi.org/10.3390/molecules25112553. https://www.osti.gov/servlets/purl/1815837.
@article{osti_1815837,
title = {Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles},
author = {Ting, Jeffrey M. and Marras, Alexander E. and Mitchell, Joseph D. and Campagna, Trinity R. and Tirrell, Matthew V.},
abstractNote = {A series of model polyelectrolyte complex micelles (PCMs) was prepared to investigate the consequences of neutral and zwitterionic chemistries and distinct charged cores on the size and stability of nanocarriers. Using aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization, we synthesized a well-defined diblock polyelectrolyte system, poly(2-methacryloyloxyethyl phosphorylcholine methacrylate)-block-poly((vinylbenzyl) trimethylammonium) (PMPC-PVBTMA), at various neutral and charged block lengths to compare directly against PCM structure–property relationships centered on poly(ethylene glycol)-block-poly((vinylbenzyl) trimethylammonium) (PEG-PVBTMA) and poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLK). After complexation with a common polyanion, poly(sodium acrylate), the resulting PCMs were characterized by dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). We observed uniform assemblies of spherical micelles with a diameter ~1.5–2× larger when PMPC-PVBTMA was used compared to PEG-PLK and PEG-PVBTMA via SAXS and DLS. In addition, PEG-PLK PCMs proved most resistant to dissolution by both monovalent and divalent salt, followed by PEG-PVBTMA then PMPC-PVBTMA. All micelle systems were serum stable in 100% fetal bovine serum over the course of 8 h by time-resolved DLS, demonstrating minimal interactions with serum proteins and potential as in vivo drug delivery vehicles. This thorough study of the synthesis, assembly, and characterization of zwitterionic polymers in PCMs advances the design space for charge-driven micelle assemblies.},
doi = {10.3390/molecules25112553},
journal = {Molecules},
number = 11,
volume = 25,
place = {United States},
year = {Sat May 30 00:00:00 EDT 2020},
month = {Sat May 30 00:00:00 EDT 2020}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Molecular engineering solutions for therapeutic peptide delivery
journal, January 2017
- Acar, Handan; Ting, Jeffrey M.; Srivastava, Samanvaya
- Chemical Society Reviews, Vol. 46, Issue 21
Preparation and characterization of poly(2-methacryloyloxyethyl phosphorylcholine)-block-poly(D,L-lactide) polymer nanoparticles
journal, January 2007
- Hsiue, Ging-Ho; Lo, Chun-Liang; Cheng, Ching-Hao
- Journal of Polymer Science Part A: Polymer Chemistry, Vol. 45, Issue 4
Analysis of Macromolecular Polydispersity in Intensity Correlation Spectroscopy: The Method of Cumulants
journal, December 1972
- Koppel, Dennis E.
- The Journal of Chemical Physics, Vol. 57, Issue 11
Structural Evolution of Polyelectrolyte Complex Core Micelles and Ordered-Phase Bulk Materials
journal, November 2014
- Krogstad, Daniel V.; Lynd, Nathaniel A.; Miyajima, Daigo
- Macromolecules, Vol. 47, Issue 22
Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives
journal, July 2010
- Knop, Katrin; Hoogenboom, Richard; Fischer, Dagmar
- Angewandte Chemie International Edition, Vol. 49, Issue 36
Poly(2-methacryloyloxyethyl phosphorylcholine) for Protein Conjugation
journal, October 2008
- Lewis, Andrew; Tang, Yiqing; Brocchini, Steve
- Bioconjugate Chemistry, Vol. 19, Issue 11
Effect of Charged Segment Length on Physicochemical Properties of Core−Shell Type Polyion Complex Micelles from Block Ionomers
journal, July 2003
- Harada, Atsushi; Kataoka, Kazunori
- Macromolecules, Vol. 36, Issue 13
Dimension of Poly(2-methacryloyloxyethyl phosphorylcholine) in Aqueous Solutions with Various Ionic Strength
journal, November 2006
- Matsuda, Yasuhiro; Kobayashi, Motoyasu; Annaka, Masahiko
- Chemistry Letters, Vol. 35, Issue 11
Raman Spectroscopic Study on the Structure of Water in Aqueous Polyelectrolyte Solutions
journal, October 2000
- Kitano, Hiromi; Sudo, Kurao; Ichikawa, Ken
- The Journal of Physical Chemistry B, Vol. 104, Issue 47
Polyelectrolyte–protein complexes
journal, August 2005
- Cooper, C. L.; Dubin, P. L.; Kayitmazer, A. B.
- Current Opinion in Colloid & Interface Science, Vol. 10, Issue 1-2
Gel phase formation in dilute triblock copolyelectrolyte complexes
journal, February 2017
- Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.
- Nature Communications, Vol. 8, Issue 1
A data ecosystem to support machine learning in materials science
journal, October 2019
- Blaiszik, Ben; Ward, Logan; Schwarting, Marcus
- MRS Communications, Vol. 9, Issue 4
Effect of water-soluble phospholipid polymers conjugated with papain on the enzymatic stability
journal, January 2004
- Miyamoto, Daisuke; Watanabe, Junji; Ishihara, Kazuhiko
- Biomaterials, Vol. 25, Issue 1
Zwitterionic Nanocarrier Surface Chemistry Improves siRNA Tumor Delivery and Silencing Activity Relative to Polyethylene Glycol
journal, May 2017
- Jackson, Meredith A.; Werfel, Thomas A.; Curvino, Elizabeth J.
- ACS Nano, Vol. 11, Issue 6
Nonviral Gene Delivery with Cationic Glycopolymers
journal, April 2019
- Van Bruggen, Craig; Hexum, Joseph K.; Tan, Zhe
- Accounts of Chemical Research
Zwitteration: Coating Surfaces with Zwitterionic Functionality to Reduce Nonspecific Adsorption
journal, April 2014
- Schlenoff, Joseph B.
- Langmuir, Vol. 30, Issue 32
Regularized Positive Exponential Sum (REPES) Program - A Way of Inverting Laplace Transform Data Obtained by Dynamic Light Scattering
journal, January 1995
- Jakeš, Jaromír
- Collection of Czechoslovak Chemical Communications, Vol. 60, Issue 11
Non-equilibrium phenomena and kinetic pathways in self-assembled polyelectrolyte complexes
journal, October 2018
- Wu, Hao; Ting, Jeffrey M.; Werba, Olivia
- The Journal of Chemical Physics, Vol. 149, Issue 16
Synthesis and Solution Properties of Zwitterionic Polymers †
journal, November 2002
- Lowe, Andrew B.; McCormick, Charles L.
- Chemical Reviews, Vol. 102, Issue 11
Critical update on 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer science
journal, January 2015
- Goda, Tatsuro; Ishihara, Kazuhiko; Miyahara, Yuji
- Journal of Applied Polymer Science, Vol. 132, Issue 16
Revolutionary advances in 2‐methacryloyloxyethyl phosphorylcholine polymers as biomaterials
journal, February 2019
- Ishihara, Kazuhiko
- Journal of Biomedical Materials Research Part A, Vol. 107, Issue 5
Kinetics of Morphological Transition between Cylindrical and Spherical Micelles in a Mixture of Anionic–Neutral and Cationic–Neutral Block Copolymers Studied by Time-Resolved SAXS and USAXS
journal, May 2018
- Takahashi, Rintaro; Narayanan, Theyencheri; Yusa, Shin-ichi
- Macromolecules, Vol. 51, Issue 10
Engineering Peptide-Based Polyelectrolyte Complexes with Increased Hydrophobicity
journal, March 2019
- Tabandeh, Sara; Leon, Lorraine
- Molecules, Vol. 24, Issue 5
Bulk and nanoscale polypeptide based polyelectrolyte complexes
journal, January 2017
- Marciel, Amanda B.; Chung, Eun Ji; Brettmann, Blair K.
- Advances in Colloid and Interface Science, Vol. 239
Irena : tool suite for modeling and analysis of small-angle scattering
journal, February 2009
- Ilavsky, Jan; Jemian, Peter R.
- Journal of Applied Crystallography, Vol. 42, Issue 2
Effect of Ionic Group on the Complex Coacervate Core Micelle Structure
journal, March 2019
- Heo, Tae-Young; Kim, Inhye; Chen, Liwen
- Polymers, Vol. 11, Issue 3
Structure–Property Relationships of Oligonucleotide Polyelectrolyte Complex Micelles
journal, October 2018
- Lueckheide, Michael; Vieregg, Jeffrey R.; Bologna, Alex J.
- Nano Letters, Vol. 18, Issue 11
Assembly and Characterization of Polyelectrolyte Complex Micelles
journal, January 2020
- Marras, Alexander E.; Vieregg, Jeffrey R.; Tirrell, Matthew V.
- Journal of Visualized Experiments, Issue 157
Dataset for Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles
dataset, January 2020
- Ting, Jeffrey; Marras, Alexander; Mitchell, Joseph
- Materials Data Facility
Therapeutic Protein–Polymer Conjugates: Advancing Beyond PEGylation
journal, September 2014
- Pelegri-O’Day, Emma M.; Lin, En-Wei; Maynard, Heather D.
- Journal of the American Chemical Society, Vol. 136, Issue 41
50th Anniversary Perspective : A Perspective on Polyelectrolyte Solutions
journal, December 2017
- Muthukumar, M.
- Macromolecules, Vol. 50, Issue 24
Zwitterionic Polymers Exhibiting High Resistance to Nonspecific Protein Adsorption from Human Serum and Plasma
journal, May 2008
- Ladd, Jon; Zhang, Zheng; Chen, Shengfu
- Biomacromolecules, Vol. 9, Issue 5
Polyelectrolyte Complexation of Oligonucleotides by Charged Hydrophobic—Neutral Hydrophilic Block Copolymers
journal, January 2019
- Marras, Alexander E.; Vieregg, Jeffrey R.; Ting, Jeffrey M.
- Polymers, Vol. 11, Issue 1
Mechanism of Dissociation Kinetics in Polyelectrolyte Complex Micelles
journal, January 2020
- Wu, Hao; Ting, Jeffrey M.; Tirrell, Matthew V.
- Macromolecules, Vol. 53, Issue 1
Self-Assembly, Antipolyelectrolyte Effect, and Nonbiofouling Properties of Polyzwitterions
journal, April 2006
- Georgiev, George S.; Kamenska, Elena B.; Vassileva, Elena D.
- Biomacromolecules, Vol. 7, Issue 4
Antifouling Stripes Prepared from Clickable Zwitterionic Copolymers
journal, July 2017
- Sae-ung, Pornpen; Kolewe, Kristopher W.; Bai, Ying
- Langmuir, Vol. 33, Issue 28
Evasion of the Accelerated Blood Clearance Phenomenon by Coating of Nanoparticles with Various Hydrophilic Polymers
journal, August 2010
- Ishihara, Tsutomu; Maeda, Taishi; Sakamoto, Haruka
- Biomacromolecules, Vol. 11, Issue 10
Synthesis and Assembly of Designer Styrenic Diblock Polyelectrolytes
journal, May 2018
- Ting, Jeffrey M.; Wu, Hao; Herzog-Arbeitman, Abraham
- ACS Macro Letters, Vol. 7, Issue 6
Complex coacervate core micelles
journal, March 2009
- Voets, Ilja K.; de Keizer, Arie; Cohen Stuart, Martien A.
- Advances in Colloid and Interface Science, Vol. 147-148
Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity
journal, December 2011
- Keefe, Andrew J.; Jiang, Shaoyi
- Nature Chemistry, Vol. 4, Issue 1
How Corona Formation Impacts Nanomaterials as Drug Carriers
journal, January 2020
- Gupta, Munishwar Nath; Roy, Ipsita
- Molecular Pharmaceutics, Vol. 17, Issue 3
Polymer physics of intracellular phase transitions
journal, November 2015
- Brangwynne, Clifford P.; Tompa, Peter; Pappu, Rohit V.
- Nature Physics, Vol. 11, Issue 11
Accelerated Blood Clearance Phenomenon Upon Repeated Injection of PEG-modified PLA-nanoparticles
journal, July 2009
- Ishihara, Tsutomu; Takeda, Miho; Sakamoto, Haruka
- Pharmaceutical Research, Vol. 26, Issue 10
Macro- and Microphase Separated Protein-Polyelectrolyte Complexes: Design Parameters and Current Progress
journal, March 2019
- Horn, Justin; Kapelner, Rachel; Obermeyer, Allie
- Polymers, Vol. 11, Issue 4
The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation
journal, February 2020
- Hoang Thi, Thai Thanh; Pilkington, Emily H.; Nguyen, Dai Hai
- Polymers, Vol. 12, Issue 2
Beyond Unpredictability: The Importance of Reproducibility in Understanding the Protein Corona of Nanoparticles
journal, August 2018
- Galmarini, Sandra; Hanusch, Usawadee; Giraud, Manon
- Bioconjugate Chemistry, Vol. 29, Issue 10
Effect of temperature on the structure and dynamics of triblock polyelectrolyte gels
journal, October 2018
- Rahalkar, Anand; Wei, Guangmin; Nieuwendaal, Ryan
- The Journal of Chemical Physics, Vol. 149, Issue 16
Advancing Polymeric Delivery Systems Amidst a Nucleic Acid Therapy Renaissance
journal, October 2013
- Burke, Paul A.; Pun, Suzie H.; Reineke, Theresa M.
- ACS Macro Letters, Vol. 2, Issue 10
Facile Synthesis of Well-Defined Hydrophilic Methacrylic Macromonomers Using ATRP and Click Chemistry
journal, November 2008
- Topham, Paul D.; Sandon, Nicolas; Read, Elizabeth S.
- Macromolecules, Vol. 41, Issue 24
Reductively Responsive Gel Capsules Prepared Using a Water-Soluble Zwitterionic Block Copolymer Emulsifier
journal, July 2018
- Nakaura, Hiroshi; Kawamura, Akifumi; Miyata, Takashi
- Langmuir, Vol. 35, Issue 5
Wormlike micelles: where do we stand? Recent developments, linear rheology and scattering techniques
journal, January 2007
- Dreiss, C?cile A.
- Soft Matter, Vol. 3, Issue 8
Transient network topology of interconnected polyelectrolyte complex micelles
journal, January 2011
- Lemmers, Marc; Voets, Ilja K.; Cohen Stuart, Martien A.
- Soft Matter, Vol. 7, Issue 4
Enrichment and Distribution of Pb 2+ Ions in Zwitterionic Poly(cysteine methacrylate) Brushes at the Solid–Liquid Interface
journal, December 2019
- He, Qiming; Qiao, Yijun; Mandia, David J.
- Langmuir, Vol. 35, Issue 52
Micro- to macro-phase separation transition in sequence-defined coacervates
journal, January 2020
- Sing, Charles E.
- The Journal of Chemical Physics, Vol. 152, Issue 2
Molecular Understanding and Design of Zwitterionic Materials
journal, November 2014
- Shao, Qing; Jiang, Shaoyi
- Advanced Materials, Vol. 27, Issue 1
The effects of poly(zwitterions)s versus poly(ethylene glycol) surface coatings on the biodistribution of protein nanoparticles
journal, January 2016
- Wang, Jing; Yuan, Shanmei; Zhang, Yajun
- Biomaterials Science, Vol. 4, Issue 9
Nanocarriers with tunable surface properties to unblock bottlenecks in systemic drug and gene delivery
journal, September 2015
- Zou, Haijuan; Wang, Zhongjuan; Feng, Min
- Journal of Controlled Release, Vol. 214
Detailed study of the reversible addition–fragmentation chain transfer polymerization and co-polymerization of 2-methacryloyloxyethyl phosphorylcholine
journal, January 2011
- Bhuchar, Neha; Deng, Zhicheng; Ishihara, Kazuhiko
- Polym. Chem., Vol. 2, Issue 3
The Materials Data Facility: Data Services to Advance Materials Science Research
journal, July 2016
- Blaiszik, B.; Chard, K.; Pruyne, J.
- JOM, Vol. 68, Issue 8
Facile Synthesis of Well-Defined, Biocompatible Phosphorylcholine-Based Methacrylate Copolymers via Atom Transfer Radical Polymerization at 20 °C
journal, August 2001
- Lobb, Emma J.; Ma, Iris; Billingham, Norman C.
- Journal of the American Chemical Society, Vol. 123, Issue 32
Interparticle Interactions in Dilute Solutions of Polyelectrolyte Complex Micelles
journal, June 2019
- Wu, Hao; Ting, Jeffrey M.; Weiss, Thomas M.
- ACS Macro Letters, Vol. 8, Issue 7
Charge-Density-Dominated Phase Behavior and Viscoelasticity of Polyelectrolyte Complex Coacervates
journal, June 2019
- Huang, Jun; Morin, Frances J.; Laaser, Jennifer E.
- Macromolecules, Vol. 52, Issue 13
On the Stability and Morphology of Complex Coacervate Core Micelles: From Spherical to Wormlike Micelles
journal, September 2012
- van der Kooij, Hanne M.; Spruijt, Evan; Voets, Ilja K.
- Langmuir, Vol. 28, Issue 40
Design of polymeric nanoparticles for biomedical delivery applications
journal, January 2012
- Elsabahy, Mahmoud; Wooley, Karen L.
- Chemical Society Reviews, Vol. 41, Issue 7
Influence of Dipole Orientation on Solution Properties of Polyzwitterions
journal, January 2016
- Morozova, S.; Hu, G.; Emrick, T.
- ACS Macro Letters, Vol. 5, Issue 1
Glucose-Functionalized, Serum-Stable Polymeric Micelles from the Combination of Anionic and RAFT Polymerizations
journal, May 2012
- Yin, Ligeng; Dalsin, Molly C.; Sizovs, Antons
- Macromolecules, Vol. 45, Issue 10