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pH-responsive iron manganese silicate nanoparticles as T1-T2* dual-modal imaging probes for tumor diagnosis
Jian Chen1, Wei-Jie Zhang, Zhen Guo
1Hefei National Laboratory for Physical Sciences at Microscale, Collaborative Innovation Center of Suzhou Nano Science and Technology, Department of Materials Science & Engineering, CAS High Magnetic Field Laboratory, University of Science and Technology of China , Hefei 230026, China.
Abstract:
Magnetic resonance imaging (MRI) probes can be concentrated in tumors through grafting targeting agents. However, the clinical application of such targeted MRI probes is largely limited because specific agents are only used to target specific characteristics of cancer cells. The development of the MRI probes that can be used regardless of tumor types or their developmental stages is highly appreciated. The acidic tumor microenvironments and acidic organelles (endosomes/lysosomes) in cancer cells are universal phenomena of solid tumors, and nanoparticles can also accumulate in tumor tissues by enhanced permeability and retention (EPR) effect. Here, we reported the synthesis of pH-responsive T1-T2* dual-modal contrast agents based on iron manganese silicate (FeMn(SiO4)) hollow nanospheres, which can release Mn(2+) ions in acidic environments, exhibiting excellent ability as agents for magnetic resonance and red fluorescence imaging. MRI for mouse models revealed that the nanoprobes could accumulate in tumors via EPR effect and then distinguish tumors from normal tissues with the synergistic effect of T1 and T2* signal only 10 min after intravenous injection. Fluorescence imaging demonstrated that the nanoprobes could be endocytosed into cancer cells and located at their lower pH compartments. Moreover, the hollow nanospheres showed no obvious toxicity and inflammation to the major organs of mice, which made them attractive diagnostic agents for different types of cancers.
Insights
New pH-responsive iron manganese silicate nanoprobes offer dual-modal imaging for various cancers. These probes accumulate in tumors and release manganese ions in acidic environments, enabling effective tumor visualization.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Medical Imaging
Background:
- Targeted magnetic resonance imaging (MRI) probes face limitations due to cancer-specific targeting agents.
- Universal acidic tumor microenvironments and enhanced permeability and retention (EPR) effect offer alternative targeting strategies.
Purpose of the Study:
- To develop universal MRI probes for various cancer types and stages.
- To create pH-responsive T1-T2* dual-modal contrast agents for enhanced tumor detection.
Main Methods:
- Synthesis of iron manganese silicate (FeMn(SiO4)) hollow nanospheres as pH-responsive contrast agents.
- Evaluation of nanoprobes' performance in MRI and fluorescence imaging in mouse models.
- Assessment of nanoprobes' biodistribution, toxicity, and inflammatory response.
Main Results:
- Nanoprobes accumulated in tumors via EPR effect and exhibited T1-T2* synergistic signals for distinguishing tumors within 10 minutes.
- Acidic environments triggered Mn(2+) ion release, enabling effective MRI and red fluorescence imaging.
- Nanoprobes were endocytosed into cancer cells, localizing in acidic endosomal/lysosomal compartments with no observed toxicity.
Conclusions:
- pH-responsive FeMn(SiO4) hollow nanospheres serve as effective dual-modal contrast agents for cancer diagnosis.
- The developed nanoprobes demonstrate potential for broad clinical application across different cancer types and stages.
- The synergistic T1-T2* imaging and low toxicity profile make these nanoprobes attractive for future cancer diagnostics.
