Tumor Acid Microenvironment-Triggered Self-Assembly of ESIONPs for T1/T2 Switchable Magnetic Resonance Imaging

Smart magnetic resonance imaging (MRI) contrast agents (CAs), whose MRI contrasting enhancement is variable in response to the specific stimulus from tumor tissues, possess great potential in precise tumor diagnosis. Herein, we design a type of extremely small iron oxide nanoparticle (ESIONP)-based pHresponsive system for activatable T-2 MRI in the tumor acid microenvironment. The ESIONP system is composed of ESIONPPEG-PGA and ESIONP-PEG-PDC, which were respectively constructed through the surface modification with poly (L-glutamic acid) (PGA) and poly(N-{N'-[N ''-(2-carbox aminoethyl)]-2-aminoethyl}glutamide) (PDC) on the surface of ESIONP. The pH-responsive system exhibits the dispersed state under the neutral condition, and when it is exposed to the weakly acid environment, ESIONP-PEG-PDC switches from the neutral to positive charge, finally leading to the aggregation by the electrostatic interaction between the positively charged ESIONP-PEG-PDC and negatively charged ESIONP-PEG-PGA. On the basis of the aggregation, the T-1 contrasting effect of the pH-responsive system switches to a T-2 contrasting effect, which can be employed to realize the selective enhancement of imaging contrast at the tumor location owing to the weakly acid microenvironment. Moreover, on the basis of size increase originated from the aggregation effect, the residence time of extremely small iron oxide nanoparticles (ESIONPs) in the tumor site is effectively prolonged, which is beneficial for the MRI of tumors. Therefore, the pH-responsive system based on the ESIONPs is a potential smart MRI contrast agent for accurate tumor diagnosis.