FeS@BSA Nanoclusters to Enable H2S-Amplified ROS-Based Therapy with MRI Guidance
Congkun Xie1, Dong Cen2, Zhaohui Ren1
1State Key Laboratory of Silicon Materials School of Materials Science and Engineering Zhejiang University Hangzhou Zhejiang 310027 P. R. China.
Abstract:
Therapeutic systems to induce reactive oxygen species (ROS) have received tremendous success in the research of tumor theranostics, but suffered daunting challenges in limited efficacy originating from low presence of reactants and reaction kinetics within cancer cells. Here, ferrous sulfide-embedded bovine serum albumin (FeS@BSA) nanoclusters, in an amorphous nature, are designed and synthesized via a self-assembly approach. In acidic conditions, the nanoclusters degrade and simultaneously release H2S gas and Fe2+ ions. The in vitro study using Huh7 cancer cells reveals that Fe2+ released from FeS@BSA nanoclusters induces the toxic hydroxyl radical (·OH) effectively via the Fenton reaction. More interestingly, H2S gas released intracellularly presents the specific suppression effect to catalase activity of cancer cells, resulting in the promoted presence of H2O2 that facilitates the Fenton reaction of Fe2+ and consequently promotes ROS induction within the cells remarkably. After intravenous administration, the nanoclusters accumulate in the tumors of mice via the enhanced permeability and retention effect and present strong magnetic resonance imaging (MRI) signals. The findings confirm this therapeutic system can enable superior anti-tumor performance with MRI guidance and negligible side effects. This study, therefore, offers an alternative gas-amplified ROS-based therapeutic platform for synergetic tumor treatment.
Insights
New FeS@BSA nanoclusters release H2S and Fe2+ to boost cancer cell reactive oxygen species (ROS) for enhanced tumor theranostics and MRI imaging.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Theranostics
Background:
- Reactive oxygen species (ROS) are crucial for tumor theranostics, but limited efficacy arises from low reactant presence and kinetics within cancer cells.
- Developing novel nanocarriers that enhance ROS generation and tumor targeting is essential for improved cancer treatment.
- Current theranostic systems face challenges in overcoming the tumor microenvironment's limitations for effective ROS induction.
Purpose of the Study:
- To design and synthesize novel amorphous ferrous sulfide-embedded bovine serum albumin (FeS@BSA) nanoclusters for enhanced tumor theranostics.
- To investigate the synergistic effect of H2S gas and Fe2+ ions released from FeS@BSA nanoclusters on ROS generation in cancer cells.
- To evaluate the anti-tumor efficacy and magnetic resonance imaging (MRI) capabilities of FeS@BSA nanoclusters in vivo.
Main Methods:
- Amorphous FeS@BSA nanoclusters were synthesized using a self-assembly approach.
- In vitro studies utilized Huh7 cancer cells to assess Fe2+-induced hydroxyl radical (·OH) generation via the Fenton reaction and H2S-mediated catalase inhibition.
- In vivo studies involved intravenous administration in mice to evaluate tumor accumulation, anti-tumor performance, and MRI signal detection.
Main Results:
- FeS@BSA nanoclusters effectively released H2S gas and Fe2+ ions in acidic conditions.
- Fe2+ ions induced ·OH via the Fenton reaction, while released H2S suppressed catalase activity, promoting H2O2 levels and further enhancing ROS induction.
- In vivo studies demonstrated tumor accumulation via the enhanced permeability and retention (EPR) effect, strong MRI signals, and significant anti-tumor efficacy with minimal side effects.
Conclusions:
- FeS@BSA nanoclusters provide a dual-action therapeutic system by amplifying ROS generation through H2S and Fe2+ synergistic effects.
- This novel platform enables effective tumor theranostics with MRI guidance and demonstrates potential for superior anti-tumor performance.
- The gas-amplified ROS-based therapeutic strategy offers a promising alternative for synergistic tumor treatment.
