Researchers have discovered that copper-based nanocapsules can significantly enhance the effectiveness of radiotherapy, offering a promising new approach to cancer treatment, especially for recurrent and metastatic cases.
Overcoming Radiation Resistance
Radiation resistance is a common phenomenon in clinical cancer management, re-irradiation of the recurrent tumor becomes an important issue[9], which accounts in part for acquired radiation resistance of tumor cells as well as the advanced molecular mechanism associated only with the radio-resistance, especially targeting aged and senescent populations. Here we demonstrate that cuproptosis is a previously undescribed system in human cancer cell (HCC) death, and it can be exploited to sensitize HCC cells to radiation.
Researchers have created programmable nanocapsules capable of introducing only copper radiotherapy-releasing molecules in tumor cells by designing and manufacturing a copper polyoxometalate named PWCu. The loss of xCT in MCF7 cells and the subsequent Cu accumulation in high-dose (8 Gy) irradiated region, represent a radiotherapy-specific trigger for: 1) Cells killing through a non-xCT/xANEO-independent pathway, and 2) The copper-mediated enhancement of local antitumor effects of radiotherapy by inducing cuproptosis.
Activating Systemic Immunity
Besides local effects, PWCu nanocapsules also establish an abscopal effect enabling induced immunogenic cell death (ICD) and thus sparking antitumor immunity. In addition to complementing the direct effects of radiotherapy, this multimodality approach leverages immune-system response factors to fight the disease.
In present work, we report the applications of advanced analytical techniques with synchrotron radiation facilities in research on dynamics between copper ions and tumor tissue via which important insights into the structure-function relationships as well as metabolic reaction of copper-based radiosensitizers were gained. The identification of the dose range where an experimental therapeutic could avoid, or have minimal effects on off target sites is paramount for preclinical safety and pharmacokinetic assessment.
Conclusion
In conclusion, we discovered novel radiosensitizer based on copper nanocapsules and presented promising approach to deal with the clinical challenge of re-irradiation in cancer patients. This new concept has the ability to improve patient outcomes through cuproptosis and systemic immune activation, particularly in patients with residual and metastatic diseases. These advanced analytical methods are valuable tools for more in-depth studies related to future therapeutic strategies of copper-based cancer treatment.
