Synergistic regulation of longitudinal and transverse relaxivity of extremely small iron oxide nanoparticles (ESIONPs) using pH-responsive nanoassemblies

Abstract

Extremely small iron oxide nanoparticles (ESIONPs), as a kind of the special T₁ magnetic resonance imaging (MRI) contrast agent that can provide T₁ contrasting enhancement since their magnetically disordered shells are dominant compared to their magnetic cores and have powerful potential for constructing stimuli-responsive contrast agents (CAs) to realize precise the tumor diagnosis with high specificity and sensitivity. The stimuli-responsive function of ESIONPs-based CAs can be directly endowed through the synergistic regulation of the longitudinal and transverse relaxivity (r₁ and r₂) of ESIONPs. However, the systematical investigation for the synergistic regulation of r₁ and r₂ of ESIONPs is quite lacking. Herein, based on the relaxivity theories, three kinds of ESIONPs-based nanoassemblies with pH-responsiveness were designed and constructed to explore the possibility of various synergistic regulations on r₁ and r₂. When three kinds of ESIONPs-based nanoassemblies were converted to dissociated ones under a weak acid environment, ESIONPs micelle could realize a synergistic regulation of the single r₂ decrease along with the stable r₁, while gold nanoparticles-ESIONPs (AuNPs-ESIONPs) vesicle could provide a synergistic regulation comprising the single r₁ increase along with the stable r₂, and ESIONPs vesicle could offer a synergistic regulation involving the r₂ decrease together with the r₁ increase. Moreover, all the synergistic regulations on r₁ and r₂ were efficient strategies to fabricate ESIONPs-based CAs with the stimuli-responsive function. These systematic and feasible synergistic regulations of r₁ and r₂ may guide and promote the development of ESIONPs-based stimuli-responsive CAs for the highly sensitive and specific tumor diagnosis.