A research team led by Prof. WU Zhengyan from the Hefei Institutes of Physical Science of the Chinese Academy of Sciences, in collaboration with Binzhou Medical University, has developed a nanostructure that improves the detection and treatment of tumors.

Their work, published in Small, focuses on creating a highly specific method for diagnosing and treating tumors using a combination of magnetic resonance imaging and enzyme activity.

A certain chemical reaction, called the metal ion-mediated Fenton-like reaction, can rapidly increase the level of harmful reactive oxygen species and slow down tumor growth, and cooper-based nanozymes, which have high catalytic activity and respond well to the tumor environment, are not very stable.Therefore, developing a tumor microenvironment-responsive core-shell nano-theranostic agent not only enables early tumor diagnosis and treatment efficacy monitoring, but also protects copper-based nanoenzymes from deactivation due to steric hindrance.

To address this issue, the research team developed a specialized nanoenzyme called CuMnO@Fe₃O₄ (CMF) with a core-shell structure that responds to the tumor microenvironment. They then attached platelet-derived growth factor receptor-β-recognizing cyclic peptide (PDGFB)-targeting ligands to the surface of CMF, creating a tumor-specific nanoenzyme known as PCMF. The core-shell design of PCMF prevents interference from thiol groups found in large molecules during circulation in the bloodstream. This enhances the anti-tumor activity of PCMF.

PCMF exhibits both T1 and T2 dual contrast imaging capabilities when activated by weak acid and glutathione. This means it can provide enhanced imaging contrast for the diagnosis of tumors.

In addition, PCMF degrades in the tumor microenvironment, releasing metal ions and ultrafine iron oxide. This process consumes glutathione, accelerates Fenton and Fenton-like reactions, increases intracellular reactive oxygen species levels, and induces apoptosis and ferroptosis in cancer cells.

PCMF also possesses photothermal conversion capability, so it can be used for combined photothermal and nanocatalytic therapy to enhance anti-cancer activity.

This work provides insights into achieving highly sensitive tumor-specific therapeutic diagnosis, according to the team.

 Schematic illustration. (Image by XIE Wenteng)