A recent article in Advanced Functional Materials explored the use of MXene-based nanozymes for bioelectricity applications in cancer therapy.
MXenes are a class of two-dimensional transition metal carbides noted for their high conductivity and biocompatibility. These properties make them promising candidates for biomedical applications.
In this study, the researchers focused on the electrochemical and nanozymatic properties of MXene in order to enhance cancer treatment through electrical pulse therapy.
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Background
MXenes have attracted attention because of their high surface area, favorable electrochemical traits, and ease of surface modification. As nanozymes, MXenes can mimic enzyme activity for both catalysis and therapeutic purposes.
Previous research has shown that electrical stimulation can promote cancer cell death by inducing apoptosis and necrosis. Electrotherapy has also been used to improve drug delivery and boost the effect of chemotherapeutics. However, the mechanisms by which MXene nanozymes affect cellular responses remain unclear.
This study aimed to fill that gap by examining how electrical pulses combined with MXene nanozymes can induce antitumor effects.
The Current Study
The researchers used a systematic approach that included both in vitro and in vivo experiments. For the electrochemical analysis, a three-electrode system was utilized with a reference, working, and counter electrode.
This setup was used to examine the dynamic current behavior of the MXene-based nanozyme (termed "MXenzyme") in an aqueous solution at different concentrations. Cyclic voltammetry was employed to determine the redox characteristics, showing how current responses changed with increased enzyme concentration.
For the in vitro component, cancer cell lines were exposed to electrical pulses at defined intensities and durations. The treatment regimen varied the number of pulses and voltage gradients. The cells were then evaluated for signs of apoptosis and necrosis using assays such as Annexin-V/PI staining and Trypan blue exclusion.
The in vivo study involved an N1S1 orthotopic hepatocellular carcinoma (HCC) rat model. N1S1 cells were injected into the liver of Sprague-Dawley rats, and standard post-operative care, including analgesic administration, was provided.
Tumor tissues were collected for histological analysis. The researchers used staining methods, including H&E and TUNEL, to observe cellular responses to the treatment. Immunohistochemistry was also conducted to assess PD-L1 expression and other markers. Appropriate statistical tests were applied to validate the results.
Results and Discussion
The electrochemical analysis showed that the MXene nanozyme demonstrated notable catalytic activity. This activity was further enhanced when electrical stimulation was applied. In vitro assays indicated that the application of electric pulses increased cancer cell death in a dose-dependent manner.
Specifically, a higher number of pulses correlated with increased levels of apoptosis, as measured by Annexin-V staining. The data suggest that the MXene nanozyme works synergistically with electrical stimulation, possibly by boosting reactive oxygen species (ROS) production and activating apoptotic pathways.
Histological analysis from the in vivo study supported the in vitro findings. Tumor samples treated with the combination therapy displayed a high number of TUNEL-positive cells, confirming increased cell death. Immunohistochemistry revealed elevated PD-L1 levels, which could point to changes in immune response pathways.
These results indicate that MXene nanozymes can enhance the effect of bioelectric treatments and may contribute to both direct tumor cell killing and modulation of the tumor environment.
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Conclusion
This study highlights the potential of incorporating MXene-based nanozymes into bioelectricity-driven cancer therapy.
The combination of electrical pulse therapy with the catalytic properties of MXene nanozymes offers a novel treatment approach. The findings demonstrate that electrical stimulation, when paired with MXene nanozymes, leads to increased cancer cell death via enhanced ROS generation and activation of apoptotic pathways.
Future research should focus on optimizing treatment parameters, assessing long-term biocompatibility, and further elucidating the molecular mechanisms behind the observed effects. This work lays the groundwork for potential clinical applications and suggests that integrating MXene nanozymes into therapeutic strategies could improve outcomes in cancer treatment.
Journal Reference
Lee S., Kim S., et al. (2025). Electric pulse regulated MXene based nanozymes for integrative bioelectricity immuno-cancer therapy. Advanced Functional Materials. DOI: 10.1002/adfm.202420870, https://advanced.onlinelibrary.wiley.com/doi/full/10.1002/adfm.202420870