Extremely Small Iron Oxide Nanoparticles with pH-Dependent Solubility Transition as T₁/T₂ Switchable Contrast Agents for MRI

Abstract

Extremely small iron oxide nanoparticles (ESIONPs), which have a switchable contrast signal and a favorable biocompatibility, are gaining considerable attention as smart magnetic resonance imaging (MRI) contrast agents (CAs). Adaptive MRI CAs could improve the accuracy of tumor diagnosis because they realize rapid imaging signal conversion under an endogenous stimulus. Herein, based on the hydrophilic to hydrophobic transition of polymers, we propose a pH-responsive T 1 /T 2 switchable ESIONP contrast agent. ESIONPs are functionalized at the surface with adamantane groups through a polyethylene glycol (PEG) chain, and subsequently, a stimuliresponsive polymer (PSDM) with pH-dependent solubility is introduced through the host−guest interaction between adamantane and β-cyclodextrin (β-CD). The obtained ESIONPs-PEG-PSDM is equipped with remarkable pH responsiveness, which triggers the aggregation of ESIONPs under the tumor acid condition, leading to the switch from a T 1 to a T 2 contrast agent. In vivo MRI experiments show that the T 2 contrast signal is selectively enhanced at the tumor location after injection of ESIONPs-PEG-PSDM. Therefore, ESIONPs-PEG-PSDM with pH-induced hydrophilic to hydrophobic transition is a potential smart MRI contrast agent for precise tumor diagnosis.

Hypoxia-Responsive T2-to-T1 Dynamically Switchable Extremely Small Iron Oxide Nanoparticles for Sensitive Tumor Imaging In Vivo

“…In the normoxic environment, the clustered ESIONPs in the EAmP may partly hinder the water molecules accessing the inner sphere of paramagnetic iron ions, which results in a moderate hydration number for each ESIONP and a relatively low r 1 value. However, in the hypoxic environment, ESIONPs are dispersed after the dissociation of EAmP and have a high hydration number to improve the r 1 value. − Consequently, the r 1 value of EAmP exhibits a slight increase upon exposure to the mimical hypoxic environment. On the other hand, based on the quantum-mechanical outer-sphere theory (as the theoretical equations shown in the Supporting Materials), the r 2 value was influenced by the saturation magnetization ( M s ).…”

Hypoxia-Responsive Aggregation of Iron Oxide Nanoparticles for T1-to-T2 Switchable Magnetic Resonance Imaging of Tumors

“…On the one hand, the r 1 enhancement can be affected by the contribution of water molecules in the inner sphere ( r 1 IS ) and the outer sphere ( r 1 OS ). As shown by the theoretical equations in the Supporting Information, q (hydration number), τ M (residency time of water molecules in the inner sphere), and τ D (diffusion correlation time of water molecules) are the main factors that could affect the r 1 value of ESIONPs. , Since the surface of HR-ESIONPs is consistently covered with a hydrophilic polymer before and after hypoxic response, the contributing factors for the r 1 value are not influenced. Thus, the r 1 value of HR-ESIONPs in the hypoxic environment is only slightly different from that in the normoxic environment.…”

Self‐Monitoring Theranostic Nanomaterials: Emerging Visual Agents for Real‐Time Monitoring of Tumor Treatment Processes

“…Although ESIONPs were not used for therapeutic monitoring in this study, it is possible to monitor the release of drugs through MRI mode switching by adding the drug between the NPs and the surface modifier. [93,94] In summary, while less controlled and personalized, TMEbased therapy and self-monitoring can achieve efficacy at deeper tissue sites with better precision. Examples of self-monitoring treatment by TME-responsive signals are summarized in Table 3.…”

“…Although ESIONPs were not used for therapeutic monitoring in this study, it is possible to monitor the release of drugs through MRI mode switching by adding the drug between the NPs and the surface modifier. [ 93,94 ]…”