Collective Activation of MRI Agents via Encapsulation and Disease-Triggered Release

Abstract

An activation mechanism based on encapsulated ultra-small gadolinium oxide nanoparticles (Gd oxide NPs) in bioresponsive polymer capsules capable of triggered release in response to chemical markers of disease (i.e., acidic pH, H2O2) is presented. Inside the hydrophobic polymeric matrices, the Gd oxide NPs are shielded from the aqueous environment, silencing their ability to enhance water proton relaxation. Upon disassembly of the polymeric particles, activation of multiple contrast agents generates a strong positive contrast enhancement of more than one order of magnitude.

Engineering of inorganic nanoparticles as magnetic resonance imaging contrast agents

“…38,48,130 Such rapid renal clearance diminishes in vivo toxicity of NPs owing to the suppressed tissue accumulation and certainly facilitates their future clinical translation and application. In addition, ultrasmall Gd 3+ -based NPs can be integrated with additional components such as multifunctional nanoplatforms for non-targeted blood pool imaging, 40 targeted molecular imaging, 41 pH/H 2 O 2 - responsive MRI, 131 and brain tumor diagnosis and image-guided therapy. 130 …”

“…encapsulated a large number of ultra-small Gd 2 O 3 NPs in biodegradable polymer capsules, which showed extremely weak MRI contrast due to effective silencing of both inner and outer sphere relaxation. 131 The r 1 of the ultra-small Gd 2 O 3 NPs could be recovered after disassembling the large capsules under acidic conditions and/or in the presence of H 2 O 2 , which are both characteristic of many diseases such as cancer (Fig. 19a).…”

Exploiting Oxidative Microenvironments in the Body as Triggers for Drug Delivery Systems

“…For example, CdSe/ZnS quantum dots conjugated to oxidized cytochrome c; oxidation by O 2 -enhances fluorescence (113). Further along these lines, oxidation-responsive nanoparticles could also be employed to develop an ROS-detecting magnetic resonance imaging contrast system via release of Gd-based contrast agents from hydrophobic assemblies and resulting in de-quenching of contrast enhancement (188). In summary, the oxidation-sensitive chemistries described here offer exciting new prospects in the field of nanomedicine, specifically targeting microenvironments with perturbations in redox levels.…”

Redoxable heteronanocrystals functioning magnetic relaxation switch for activatable T1 and T2 dual-mode magnetic resonance imaging

“…For those nanoplatforms, however, fastidious processing of the nanoparticles and well-defined DMCA design are required to avoid quenching the T 1 and T 2 contrast effects. Furthermore, most of the contrast agents are "always ON" systems, exerting the MR contrast effect regardless of their proximity or interaction with target cells or environmental markers in biology; this can result in poor target-to-background ratios [20,21].…”