Synergistic Regulation on 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 special T1 magnetic resonance imaging (MRI) contrast agent that can provide T1 contrasting enhancement since its magnetically disordered shell is dominant compared to the magnetic core, have the powerful potential on constructing stimuli-responsive contrast agents (CAs) to realize the precise 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, systematical investigation on 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 are designed and constructed to explore the possibility of various synergistic regulations on the r1 and r2. When three kinds of ESIONPs-based nanoassemblies were converted to dissociated ones under weakly acid environment, ESIONPs micelle can realize a synergistic regulation of single r2 decrease along with stable r1, gold nanoparticles-ESIONPs (AuNPs-ESIONPs) vesicle can provide a synergistic regulation containing single r1 increase along with stable r2, and ESIONPs vesicle can offer a synergistic regulation involving r2 decrease together with r1 increase. Moreover, all the synergistic regulations on the r1 and r2 are 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.