Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

Application of Cherenkov radiation in tumor imaging and treatment.

Cherenkov radiation (CR) is the characteristic blue glow that is generated during radiotherapy or radioisotope decay. Its distribution and intensity naturally reflect the actual dose and field of radiotherapy and the location of radioisotope imaging agents in vivo. Therefore, CR can represent a potential in situ light source for radiotherapy monitoring and radioisotope-based tumor imaging. When used in combination with new imaging techniques, molecular probes or nanomedicine, CR imaging exhibits unique advantages (accuracy, low cost, convenience and fast) in tumor radiotherapy monitoring and imaging. Furthermore, photosensitive nanomaterials can be used for CR photodynamic therapy, providing new approaches for integrating tumor imaging and treatment. Here the authors review the latest developments in the use of CR in tumor research and discuss current challenges and new directions for future studies.

Cherenkov radiation (CR) is the characteristic blue glow that is generated during radiotherapy (a common treatment that uses radiation to kill cancer cells) or radioisotope decay (the process that emits radiation from radioisotopes). CR can be used for monitoring the dose and dose distribution of radiotherapy to prevent radiotherapy-related adverse events. In addition, radioisotope-induced CR can be used as a light source for locating the tumor region for tumor imaging. With a combination of imaging techniques, molecular probes and nanomedicine, CR exhibits huge potential and unique advantages (accuracy, low cost, convenience and fast) in tumor radiotherapy monitoring and imaging. Furthermore, some photosensitive nanomaterials have been developed to absorb CR to generate reactive oxygen species, which can result in cell death. This therapeutic strategy is known as CR photodynamic therapy. CR photodynamic therapy is available to integrate with radiotherapy or tumor imaging, providing new approaches for tumor diagnosis and treatment. Here the authors review the latest developments in the use of CR in tumor research and discuss current challenges and new directions for future studies.