Enhanced photodynamic therapy through multienzyme-like MOF for cancer treatment
Letian Lv1,2, Zhao Fu1, Qing You1
1CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China.
Abstract:
Overcoming resistance to apoptosis is a major challenge in cancer therapy. Recent research has shown that manipulating mitochondria, the organelles critical for energy metabolism in tumor cells, can increase the effectiveness of photodynamic therapy and trigger apoptosis in tumor cells. However, there is currently insufficient research and effective methods to exploit mitochondrial damage to induce apoptosis in tumor cells and improve the effectiveness of photodynamic therapy. In this study, we present a novel nanomedicine delivery and therapeutic system called PyroFPSH, which utilizes a nanozymes-modified metal-organic framework as a carrier. PyroFPSH exhibits remarkable multienzyme-like activities, including glutathione peroxidase (GPx) and catalase (CAT) mimicry, allowing it to overcome apoptosis resistance, reduce endogenous glutathione levels, and continuously generate reactive oxygen species (ROS). In addition, PyroFPSH can serve as a carrier for the targeted delivery of sulfasalazine, a drug that can induce mitochondrial depolarization in tumor cells, thereby reducing oxygen consumption and energy supply in the mitochondria of tumor cells and weakening resistance to other synergistic treatment approaches. Our experimental results highlight the potential of PyroFPSH as a versatile nanoplatform in cancer treatment. This study expands the biomedical applications of nanomaterials as platforms and enables the integration of various novel therapeutic strategies to synergistically improve tumor therapy. It deepens our understanding of multienzyme-mimicking active nanocarriers and mitochondrial damage through photodynamic therapy. Future research can further explore the potential of PyroFPSH in clinical cancer treatment and improve its drug loading capacity, biocompatibility and targeting specificity. In summary, PyroFPSH represents a promising therapeutic approach that can provide new insights and possibilities for cancer treatment.
Insights
This study introduces PyroFPSH, a novel nanomedicine that combats cancer by targeting mitochondria. PyroFPSH overcomes apoptosis resistance and enhances photodynamic therapy effectiveness, offering a promising new cancer treatment strategy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Apoptosis resistance is a key challenge in cancer treatment.
- Mitochondrial manipulation can enhance photodynamic therapy (PDT) efficacy.
- Effective methods to induce mitochondrial damage for apoptosis are limited.
Purpose of the Study:
- To develop a novel nanomedicine delivery system, PyroFPSH, for cancer therapy.
- To exploit mitochondrial damage to overcome apoptosis resistance and improve PDT.
- To investigate the synergistic effects of PyroFPSH with targeted drug delivery.
Main Methods:
- Utilized a nanozymes-modified metal-organic framework as a carrier for PyroFPSH.
- PyroFPSH demonstrated glutathione peroxidase (GPx) and catalase (CAT) mimicry.
- PyroFPSH delivered sulfasalazine to induce mitochondrial depolarization and reduce tumor cell oxygen consumption.
Main Results:
- PyroFPSH overcame apoptosis resistance by reducing glutathione and generating reactive oxygen species (ROS).
- Targeted delivery of sulfasalazine weakened tumor cell resistance to synergistic treatments.
- PyroFPSH showed potential as a versatile nanoplatform for integrated cancer therapy.
Conclusions:
- PyroFPSH is a promising nanoplatform for enhancing cancer treatment through mitochondrial targeting and PDT.
- This study expands nanomaterial applications in cancer therapy and deepens understanding of multienzyme-mimicking nanocarriers.
- Future research should focus on PyroFPSH's clinical translation, optimizing drug loading, biocompatibility, and targeting specificity.
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