Antiferromagnetic Pyrite as the Tumor Microenvironment‐Mediated Nanoplatform for Self‐Enhanced Tumor Imaging and Therapy

TLDR

Research has explored TME‑driven nanotheranostics, including pH‑sensitive imaging, acidity‑triggered starvation therapy, and H₂O₂‑activated chemotherapy. The study introduces a TME‑mediated nanoplatform of antiferromagnetic pyrite nanocubes that harnesses tumor‑generated peroxide for self‑enhanced MRI and combined PTT/CDT. Pyrite nanocubes oxidize in the high‑peroxide TME, generating hydroxyl radicals for chemodynamic therapy, while photothermal heating accelerates the Fenton reaction to synergistically enhance PTT/CDT. Elevated surface Fe valence improves MRI and CDT performance, and this first demonstration of a TME‑responsive valence‑variable pyrite platform establishes a new paradigm for synergistic nanotheranostics.

Abstract

Several decades of research have identified the specific tumor microenvironment (TME) to develop promising nanotheranostics, such as pH-sensitive imaging, acidity-sensitive starving therapy, and hydrogen peroxide-activated chemotherapy, etc. Herein, a novel TME-mediated nanoplatform employing antiferromagnetic pyrite nanocubes is presented, exploiting the intratumoral, overproduced peroxide for self-enhanced magnetic resonance imaging (MRI) and photothermal therapy (PTT)/chemodynamic therapy (CDT). Through the activation of excessive peroxide in the tumor microenvironment, pyrite can lead to in situ surface oxidation and generate hydroxyl radicals to kill tumor cells (i.e., CDT). The increase of the valence state of surface Fe significantly promotes the performance of MRI accompanied by CDT. Furthermore, the localized heat by photothermal treatment can accelerate the intratumoral Fenton process, enabling a synergetic PTT/CDT. To our best knowledge, this is the first study to use the TME-response valence-variable strategy based on pyrite for developing a synergetic nanotheranostic, which will open up a new dimension for the design of other TME-based anticancer strategies.