This Title All WIREs
How to cite this WIREs title:
WIREs Nanomed Nanobiotechnol
Impact Factor: 6.14

Complex coacervate‐based materials for biomedicine

Full article on Wiley Online Library:   HTML PDF

Can't access this content? Tell your librarian.

There has been increasing interest in complex coacervates for deriving and transporting biomaterials. Complex coacervates are a dense, polyelectrolyte‐rich liquid that results from the electrostatic complexation of oppositely charged macroions. Coacervates have long been used as a strategy for encapsulation, particularly in food and personal care products. More recent efforts have focused on the utility of this class of materials for the encapsulation of small molecules, proteins, RNA, DNA, and other biomaterials for applications ranging from sensing to biomedicine. Furthermore, coacervate‐related materials have found utility in other areas of biomedicine, including cartilage mimics, tissue culture scaffolds, and adhesives for wet, biological environments. Here, we discuss the self‐assembly of complex coacervate‐based materials, current challenges in the intelligent design of these materials, and their utility applications in the broad field of biomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1442. doi: 10.1002/wnan.1442 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement
Plots of turbidity showing a comparison of (a) a series of monovalent and divalent salts. (b) A plot of turbidity versus ionic strength for the salts shown in (a). Additional comparisons of a series of (c) a series of sodium halide salts and (d) other monovalent sodium salts. All samples were prepared at 1 mM total monomer concentration, 50/50 mol% poly(acrylic acid sodium salt) (pAA)/poly(allylamine hydrochloride) (pAH) ratio at pH 6.5 and complexes were prepared by adding pAA to solution containing pAH and the desired salt concentration. (Reprinted with permission from Ref . Copyright 2014 Open Access from Polymers)
[ Normal View | Magnified View ]
Turbidity plot as a function of mole fraction poly(allylamine hydrochloride) (pAH) at pH 6.5 where both pAH and poly(acrylic acid sodium chloride) (pAA) are fully charged (black circles) and pH 8.5 where pAH is only half charged (blue squares). Data are shown for no salt conditions (open symbols) and 100 mM NaCl (closed symbols). All samples were prepared at 1 mM total monomer concentration and complexes were prepared by adding pAA to solution containing pAH and the desired salt concentration. (Reprinted with permission from Ref . Copyright 2014 Open Access from Polymers)
[ Normal View | Magnified View ]
Images of complex coacervates composed of Z‐Cat‐C10, a catechol‐containing zwitterionic surfactant inspired by mussel foot protein‐5 (mfp‐5) (a) in 4‐mm‐diameter glass test tubes. The turbid dispersions of coacervate droplets (left) and the bulk‐separated phases showing the denser coalesced coacervate phase on the bottom (middle and right). The tilted tube (right) indicates the fluidity of both phases (right). (b) Cryo‐transmission electron microscopy (TEM) image of the interface between the dense coacervate phase (CoA) and the equilibrium solution (EqS). White arrows indicate same small aggregates found in both phases. (c) Optical micrographs showing the time course of the coalescence of coacervates composed of Z‐Cat‐C10. The 16 min, 4 s image shows coalescence of two droplets. (Reprinted with permission from Ref . Copyright 2015 Nature Publishing Group)
[ Normal View | Magnified View ]
Coacervate‐based strategies for sensing and detection. (a) Structure of the ligand 1,11‐bis(2,6‐dicarboxypyridin‐4‐yloxy)‐3,6,9‐trioxaundecane (L2EO4) and the diblock copolymer poly(N‐methyl‐2‐vinyl‐pyridinium iodide)‐b‐poly(ethylene oxide) (P2MVP41‐PEO205), along with a schematic representation of the formation of the corresponding Eu/Gd‐complex coacervate‐core micelles (C3Ms). (b) Luminescent emission intensity and nuclear magnetic resonance dispersion profiles of Eu/Gd‐C3Ms at different Eu3+/Gd3+ ratios. (a and b: Reprinted with permission from Ref . Copyright 2013 Royal Society of Chemistry). (c) Schematic of the lamellar poly(styrene‐b‐2‐vinylpyridine) (PS‐QP2VP) photonic gel and its two possible behaviors (swelling/contraction) in protein solutions. (d) Photos of PS‐QP2VP photonic gels after soaking in 1% protein solutions in 10 mM Tris buffer overnight. Scale bar is 1 mm. (c and d: Reprinted with permission from Ref . Copyright 2014 American Chemical Society)
[ Normal View | Magnified View ]
In vivo results from complex coacervate‐based delivery and adhesive platforms. (a) Comparison of hematoxylin and eosin (H&E; scale bar is 1 mm) and α‐actinin (scale bar is 50 µm)‐stained tissues for infarcted myocardium receiving treatments of saline, [poly(ethylene argininylaspartate diglyceride) (PEAD):heparin], free fibroblast growth factor‐2 (FGF2), and FGF2 coacervate. Application of the coacervate FGF2 formulation significantly reduced the infarct area, preventing ventricular dilation and preserving cardiac fibers, compared with the other treatment strategies. α‐Actinin‐stained tissues demonstrate enhanced preservation of cardiomyocytes in the infarct zone for the FGF2 coacervate treatment. (Reprinted with permission from Ref . Copyright 2013 Elsevier). (b) Adhesive complex coacervate adhesive analysis on skull surface (left) and CD68 immunoreactivity (green) associated with adhesive (red). Scale bars represent 500 µm. (Reprinted with permission from Ref . Copyright 2010 Elsevier)
[ Normal View | Magnified View ]
Protein encapsulation via complex coacervation. (a) Plot of changes in turbidity as a function of the ratio of negative‐to‐positive residues on the protein. The gray shaded region corresponds to proteins that do not undergo phase separation. (Reprinted with permission from Ref . Copyright 2016 Royal Society of Chemistry). (b) Encapsulation of bovine serum albumin (BSA) into a coacervate. Positively charged poly(l‐lysine) (PLys) is added to the negatively charged protein to form an intermediate complex. Negatively charged poly(d,l‐glutamate) (PGlu) is then added to form the complex coacervate. (Reprinted with permission from Ref . Copyright 2014 American Chemical Society)
[ Normal View | Magnified View ]
Architectural schemes of various hierarchically structured coacervate‐based materials including (a) bulk coacervates, (b) coacervate‐corona micelles, (c) coacervate‐core micelles, (d) coacervate‐core vesicles (also known as polyion complex vesicles or PICsomes), and triblock copolymer coacervate hydrogels with both (e) spherical and (f) hexagonal coacervate geometries.
[ Normal View | Magnified View ]
Schematic representation of a series of thermodynamic phase diagrams, or binodal curves, as a function of salt concentration and polymer concentration (for a given stoichiometry, solution pH, and temperature), defining the boundary between the two‐phase region of coacervation (beneath the curve) and the single‐phase solution region (above the curve). The critical point is indicated at the highest point of each curve. The dashed tie‐line defines the equilibrium concentration for a coexisting coacervate and supernatant phase. Increasing polymer chain length can drive an increase in the width of the two‐phase region, as indicated by the arrow. Similar trends have been observed for increasing polymer charge density.
[ Normal View | Magnified View ]
Controllable enzymatic and catalytic activity in complex coacervate domains. (a) Schematic illustration of enzyme activities during the reversible reaction using lambda protein phosphate (LPP) enzyme and protein kinase A (PKA) with adenosine diphosphate (ADP), adenosine triphosphate (ATP), and Ethylenediaminetetraacetic acid (EDTA) resulting in the formation and dissolution of a coacervate phase. (Reprinted with permission from Ref . Copyright 2015 Nature Publishing Group). (b) UV–vis spectra demonstrating the encapsulation of CMDex‐Fe3O4 (left), CMDex‐Co3O4 (middle), and gold (right) nanoparticles in poly(lysine)‐adenosine triphosphate (PLys‐ATP) droplets with accompanying optical images of the magnetic CMDex‐Fe3O4 nanoparticle system and a transmission electron microscopy (TEM) micrograph of encapsulated gold nanoparticles. (c) Plots of the change in concentration of (top) 2,2‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and bNADPH (bottom) as a function of time in both the presence (closed circles) and absence (open circles) of catalytic coacervate droplets. (b and c: Reprinted with permission from Ref . Copyright 2011 Nature Publishing Group). (d) UV–vis spectra (top) and plot of the time‐dependent changes in the normalized peak intensities (bottom) for the selective catalytic degradation of methylene blue compared with rhodamine B dye as a result of selective uptake into coacervate microdroplets formed from titania nanosheets, poly(diallyldimethylammonium) chloride, and ATP. (Reprinted with permission from Ref . Copyright 2015 Royal Society of Chemistry)
[ Normal View | Magnified View ]
Membraneless organelles form via liquid‐liquid phase separation. (a) Differential interface contrast (DIC) and fluorescence micrographs of a HeLa cell expressing Ddx4YFP. Ddx4YFP forms dense, spherical organelles in the nucleus. Cells were stained with antibodies to visualize nucleoli, promyelocytic leukemia (PML) bodies, nuclear speckles, and Cajal bodies. (Reprinted with permission from Ref . Copyright 2015 Open Access from Molecular Cell by Cell Press). (b) Time‐lapse imaging of a nuclear body assembly in transiently transfected HeLa cells expressing nephrin intracellular domain (NCID). Scale bar represents 5 µm. (Reprinted with permission from Ref . Copyright 2016 Elsevier). (c) Representative images of the morphological changes in in vitro droplets of wild‐type (WT) and G156E FUS during an ‘aging’ experiment over 8 h. (Reprinted with permission from Ref . Copyright 2015 Elsevier)
[ Normal View | Magnified View ]
The critical role of peptide chirality on complex coacervation. (a) Bright‐field optical micrographs showing the liquid coacervates or solid precipitates resulting from the stoichiometric electrostatic complexation of l, d, or racemic (d,l) poly(lysine) (single letter abbreviation K) with l, d, or racemic (d,l) poly(glutamate) (single letter abbreviation E) at a total residue concentration of 6 and 100 mM NaCl, pH 7.0. Complexes are formed from plK + plE, pdK + plE, p(d,l)K + plE, plK + pdE, pdK + pdE, p(d,l)K + pdE, plK + p(d,l)E, pdK + p(d,l)E, p(d,l)K + p(d,l)E. Liquid coacervate droplets are only observed during complexation involving a racemic polymer. Scale bars are 25 µm. (Reprinted with permission from Ref . Copyright 2015 Nature Publishing Group). (b) Secondary structure of each residue versus time for various 1‐µs molecular dynamics (MD) simulations of 10‐amino acid polypeptide pairs. ‘A’ denotes simulations containing nonhomochiral peptides of poly(glutamate) (PGlu, blue), with a specified number of continuous l amino acids in the center of the chain, in complex with a homochiral poly(l‐lysine) (PLys, red). The structures of PLys and PGlu are shown at 0, 400, 700, and 1000 ns for each pair. (Reprinted with permission from Ref . Copyright 2015 The Royal Society of Chemistry)
[ Normal View | Magnified View ]

Related Articles

Protein‐based functional nanomaterial design for bioengineering applications

Browse by Topic

Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Diagnostic Tools > In Vitro Nanoparticle-Based Sensing

Access to this WIREs title is by subscription only.

Recommend to Your
Librarian Now!

The latest WIREs articles in your inbox

Sign Up for Article Alerts