Activatable interpolymer complex-superparamagnetic iron oxide nanoparticles as magnetic resonance contrast agents sensitive to oxidative stress

Abstract

Magnetic resonance contrast agents that can be activated in response to specific triggers hold potential as molecular biosensors that may be of great utility in non-invasive disease diagnosis. We developed an activatable agent based on superparamagnetic iron oxide nanoparticles (SPIOs) that is sensitive to oxidative stress, a factor in the pathophysiology of numerous diseases. SPIOs were coated with poly(ethylene glycol) (PEG) and complexed with poly(gallol), a synthetic tannin. Hydrogen bonding between PEG and poly(gallol) creates a complexed layer around the SPIO that decreases the interaction of solute water with the SPIO, attenuating its magnetic resonance relaxivity. The complexed interpolymer nanoparticle is in an OFF state (decreased T2 contrast), where the contrast agent has a low T2 relaxivity of 7 ± 2 mM−1 s−1. In the presence of superoxides, the poly(gallol) is oxidized and the polymers decomplex, allowing solute water to again interact with the SPIO, representing an ON state (increased T2 contrast) with a T2 relaxivity of 70 ± 10 mM−1 s−1. These contrast agents show promise as effective sensors for diseases characterized in part by oxidative stress such as atherosclerosis, diabetes, and cancer.

Surface characterization of nanoparticles using near-field light scattering

“…The conjugation of BBAs used an optimized Steglich esterification to bind the carboxyl groups on the BBAs to the free hydroxyl groups on 40 kDa dextran. For this study, tribenzyloxybenzoic acid (TBBA) was used as the phenolic precursor, resulting in a polygallol polymer [ 35 – 37 ].…”

“…PEG and PEG-containing copolymers tend to increase the circulation time of nanoparticles by reducing opsonization [ 32 , 34 ]. A polymeric pseudotannin has been designed to mimic natural tannin structures and form nanoscale interpolymer complexes with PEG via hydrogen bonding as a novel coating for SPIO magnetic resonance contrast agents [ 35 – 37 ]. The stability of these complexes is highly dependent on the plurality of the hydrogen bonds between PEG and pseudotannin [ 35 – 36 ].…”

Iron Oxide Nanoparticles as Imaging and Therapeutic Agents for Atherosclerosis

“…69 Moreover, decreased eNOS activity results in the Toll-like receptor 4 mediated p38 mitogen-associated protein kinase signaling which is responsible for the production of inflammatory cytokines, upregulation of cell adhesion molecules, and production of CSFs, all of which aid in inflammation and leukocyte recruitment. 70,71 A research group developed an iron oxide-cerium oxide nanoparticle capable of interacting with ROS in vitro. 72 Cerium oxide has the ability to act as an antioxidant and convert ROS to a nonreactive compound.…”

Near Infrared-Activated Dye-Linked ZnO Nanoparticles Release Reactive Oxygen Species for Potential Use in Photodynamic Therapy

“…After optimization of sonication time, PEG (6000 MW, Alfa Aesar, Haverhill, MA, USA) was adsorbed to the surface of Dye 847-ZnO NPs. PEG is biocompatible, increases colloidal stability, and increases circulation time in vivo [56,58,62,[99][100][101][102][103][104][105][106]. Particle samples from the same stock that had been sonicated for 2 h were sonicated for 6 h (including 2 h of stock sonication), and 1.05 × 10 −3 M PEG solution was added to the nanoparticle stock (1 mg/mL).…”