Nano Imaging Technologies: Polymer vesicles loaded with precipitated gadolinium nanoparticles: A novel target-specific contrast agent for magnetic resonance imaging

Abstract

Gadolinium-based contrast agents for imaging of cellular or subcellular compartments by clinical magnetic resonance imaging (MRI) currently lack a satisfying signal-to-noise ratio and acceptable target specificity. Water-soluble enzyme nanoreactors based on amphiphilic triblock copolymer membranes functionalized with size-selective pore proteins were used to precipitate highly insoluble gadolinium phosphate nanoparticles inside the vesicles. Surface modification with the macrophage scavenger receptor A1 (SRA-1) ligand polyguanylic acid and fluorescence-labeled streptavidin resulted in a novel type of bimodal target-specific contrast agent for MR and fluorescence imaging. Physicochemical analyses showed vesicles with a mean diameter of 46 +/-9 nm and distinguishable particulate content with high electron density. In MRI, the nanocarrier displayed a T1 relaxivity of 3.5e10 L x s(-1) x mmol(-1) vesicles. Uptake to target cells and intracellular localization was proven both with confocal microscopy and MRI. In conclusion, we introduce a novel receptor-targetable gadolinium nanoparticle-based vesicular contrast agent for bimodal imaging in clinical medicine and show its use in first in vitro and cell culture experiments. Broz, P Poe, D Nanomedicine 2009, 2.2:43-48

Selective ion-permeable membranes by insertion of biopores into polymersomes

“…As a result of simultaneously possessing hydrophilic and hydrophobic molecules in a single compartment, various applications can be developed based on polymersomes. These range from drug carriers, [11][12][13] and containers for contrast agents, 14 up to nanoreactors, [15][16][17][18] and artificial organelles. 19 In addition, in a biomimetic approach, multicompartmentalized polymersomes have been introduced to allow reactions between different inner compartments encapsulated in a giant compartment.…”

Protein–polymer nanoreactors for medical applications

“…231 A promising nanoreactor to produce Gd-phosphate inside PMOXA-PDMS-PMOXA polymersomes was proposed to avoid the intrinsic toxicity of Gd ions. 232 Acid phosphatase encapsulated in polymersomes converted the substrate glucose-1-phosphate to produce phosphate ions. As Gd-phosphate is highly water-insoluble, it precipitates inside the cavity of the nanoreactor, and in this way its toxicity is significantly reduced.…”

Synthetic biology, inspired by synthetic chemistry

“…Taken together, polymersomes open new perspectives for diagnostic and theranostic applications [118][119][120] serving as a platform for combination of bioactive compounds with detection agents such as fluorescent dyes [121,122], inorganic compounds, or metal complexes [123][124][125][126][127][128]. Encapsulation inside polymersomes represents a promising way to prevent side and toxic effects of active compounds such as quantum dots or MRI contrast agents.…”