Iron phosphide nanoparticles as a pH-responsive T1 contrast agent for magnetic resonance tumor imaging

In this work, the potential of FeP nanoparticles as a pH-responsive T₁ contrast agent was investigated. The FeP nanoparticles have good biocompatibility and can significantly amplify T₁ magnetic resonance signals in response to the acidic microenvironment of solid tumors, holding great promise in serving as an acid-activatable T₁ contrast agent for tumor imaging.

In this work, the potential of FeP nanoparticles as a pH-responsive T₁ contrast agent was investigated.

Magnetic resonance imaging (MRI) is currently one of the most powerful medical imaging techniques due to its noninvasive character, deep tissue penetration, and ability to provide images with excellent anatomical details.^1–3 MRI contrast agents are a group of contrast media that can improve the accuracy and specificity of MRI.^4–6 In general, MRI contrast agents can be divided into T₁ positive contrast agents and T₂ negative contrast agents according to the relaxation processes. T₁ contrast agents shorten the longitudinal relaxation time of water protons, resulting in a brighter signal, while T₂ contrast agents reduce the transverse relaxation time, leading to a darker signal.^7,8 Nanomaterials containing paramagnetic metal ions (e.g., Gd³⁺, Mn²⁺, and Fe³⁺) have been widely used as T₁ MRI contrast agents.^9–14 On the other hand, magnetic nanoparticles with high saturation magnetization are the most commonly used as T₂ contrast agents because they can generate a local magnetic field in the presence of the external magnetic field to accelerate the dephasing of surrounding water protons.^15–17The exploitation of highly specific and sensitive imaging contrast agents is of great importance for precise disease diagnosis.¹⁸ Activatable imaging contrast agents that can respond to biological stimulis (e.g., pH, redox potential, and enzyme) to produce contrast signals, have emerged as the next generation of molecular imaging probes.^19–22 They can minimize the signal from nontarget background, therefore greatly improve the target-to-background ratio. Conventional T₁ contrast agents such as Gd₂O₃ nanoparticles and MnO nanoparticles have been demonstrated that can afford effective T₁ shortening effect to improve the visibility. However, these contrast agents continuously emit signals are “always on”, which fail to response to pathological parameters and hence lack in specificity and sensitivity. Activatable MRI contrast agents that only generate signals in response to a certain stimuli (e.g., physiological difference in pH in tumor microenvironment) thus are highly desirable, because they not only greatly enhance the specificity and sensitivity of disease diagnosis, but also potentially allow MRI to monitor biological processes.^23–25 Herein, we report a novel pH-activatable T₁ contrast agent based on FeP nanoparticles. We found that the as-synthesized FeP nanoparticles can respond to the acidic microenvironment of solid tumor to produce significant T₁ contrast enhancement by releasing paramagnetic Fe ions. Furthermore, both in vitro and in vivo investigations indicate that the FeP nanoparticles have good biocompatibility that show no obvious cytotoxicity and harmful effects. Therefore, the FeP nanoparticles can potentially serve as an acid-responsive T₁ MRI contrast agent for tumor imaging.