Supramolecular Protein Cage Composite MR Contrast Agents with Extremely Efficient Relaxivity Properties

Liepold, Lars; Abedin, Joynal; Buckhouse, Emily D; Frank, Joseph A.; Young, Mark; Douglas, Trevor

doi:10.1021/nl902884p

Cited by 58 publications

(64 citation statements)

References 44 publications

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“…The Solomon-Bloembergen-Morgan model predicts that the relaxivity is dominated by three important parameters: the number of metal-bound water molecules ( q ), the mean residence lifetime for metal-bound water (s M ), and the rotational correlation time (s R ). We, and others, have effectively used this model to predict and design new contrast agents that optimize these important parameters [17, 27, 41]. Both s R and s M of free MnPP (s R = 50-80 ps, s M = 10 ns) [42] are comparable to those of free gadolinium diethylene-triaminepentaacetic acid (s R = 70 ps, s M = 16 ns) [27].…”

Section: Resultsmentioning

confidence: 99%

“…Various groups have explored dendrimers [14], liposomes [15, 16], protein cages [17, 18], and gold nanoparticles [19] as potential platforms for conjugation of small-molecule contrast agents. Virus-like particles (VLPs) derived from virus particles but devoid of their nucleic acid have an advantage over other systems because of their large macromolecular size and control over assembly, which allows high loading density of desired cargo molecules.…”

Section: Introductionmentioning

confidence: 99%

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Manganese(III) porphyrins complexed with P22 virus-like particles as T 1-enhanced contrast agents for magnetic resonance imaging

et al. 2013

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Virus-like particles are powerful platforms for the development of functional hybrid materials. Here, we have grown a cross-linked polymer (cross-linked aminoethyl methacrylate) within the confines of the bacteriophage P22 capsid (P22-xAEMA) and functionalized the polymer with various loadings of paramagnetic manganese(III) protoporphyrin IX (MnPP) complexes for evaluation as a macromolecular magnetic resonance imaging contrast agent. The resulting construct (P22-xAEMA-MnPP) has r1,particle = 7,098 mM−1 s−1 at 298 K and 2.1 T (90 MHz) for a loading of 3,646 MnPP molecules per capsid. The Solomon-Bloembergen-Morgan theory for paramagnetic relaxivity predicts conjugating MnPP to P22, a supramolecular structure, would result in an enhancement in ionic relaxivity; however, all loadings experienced low ionic relaxivities, r1,ionic, ranging from 1.45 to 3.66 mM−1 s−1, similar to the ionic relaxivity of free MnPP. We hypothesize that intermolecular interactions between neighboring MnPP molecules block access of water to the metal site, resulting in low r1,ionic relaxivities. We investigated the effect of MnPP interactions on relaxivity further by either blocking or exposing water binding sites on MnPP. On the basis of these results, future design strategies for enhanced r1,ionic relaxivity are suggested. The measured r2,ionic relaxivities demonstrated an inverse relationship between loading and relaxivity. This results in a loading-dependent r2/r1 behavior of these materials indicating synthetic control over the relaxivity properties, making them interesting alternatives to current magnetic resonance imaging contrast agents.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Manganese(III) porphyrins complexed with P22 virus-like particles as T 1-enhanced contrast agents for magnetic resonance imaging

et al. 2013

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“…142,143 In this unconventional approach, 2-poly(aminoethyl methacrylate) cross-linked with bisacrylamide was polymerized inside the cavity of the p22 virus capsid using ATRP (Fig. 7).…”

Section: Protein Nanocagesmentioning

confidence: 99%

Protein–polymer therapeutics: a macromolecular perspective

Kuan

et al. 2015

Biomater. Sci.

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The development of protein-polymer hybrids emerged several decades ago with the vision that their synergistic combination will offer macromolecular hybrids with manifold features to succeed as the next generation therapeutics. From the first generation of protein-polymer therapeutics represented by PEGylated proteins, the field has since advanced, reinforced by the progress in contemporary chemical techniques for designing polymeric scaffolds and protein engineering. Novel polymerization techniques that offer multifunctional strategies as well as a greater understanding of proteins and their biological behavior have both proven to be exceptional tools in the construction of these hybrid materials. In this review, we seek to summarize and highlight the recent progress in these semi-synthetic protein hybrids in terms of their preparation, design, resulting bioarchitectures and bioactivities for their intended bio-applications.

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“…Examples include VLPs encapsulating fluorophores for fluorescence imaging and VLPs encapsulating gadolinium or iron oxide compounds for magnetic resonance imaging (MRI) [7,[17][18][19]. However, this study represents the first time such structures have been applied as contrast agents in x-ray imaging.…”

Section: Introductionmentioning

confidence: 99%

“…Protein cage structures such as those mentioned above have been studied for their potential in materials synthesis [7,12], catalysis [13,14], drug and gene delivery [15,16], bio-imaging [17][18][19], cell targeting [20,21], and vaccine development [11]. VLPs in particular are promising, as they exist in a large range of sizes (tens to hundreds of nanometers), have well-defined, monodisperse structures, can be purified in large quantities, and can be easily modified both genetically and chemically [22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents

et al. 2014

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Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorptionbased x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based "nanobubble" contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size.

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Supramolecular Protein Cage Composite MR Contrast Agents with Extremely Efficient Relaxivity Properties

Cited by 58 publications

References 44 publications

Manganese(III) porphyrins complexed with P22 virus-like particles as T 1-enhanced contrast agents for magnetic resonance imaging

Manganese(III) porphyrins complexed with P22 virus-like particles as T 1-enhanced contrast agents for magnetic resonance imaging

Protein–polymer therapeutics: a macromolecular perspective

X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents

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