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

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.