Gadolinium Neutron Capture Reaction-Induced Nucleodynamic Therapy Potentiates Antitumor Immunity

A nuclear reaction-induced dynamic therapy, denoted as nucleodynamic therapy (NDT), has been invented that triggers immunogenic cell death and successfully treats metastatic tumors due to its unexpected abscopal effect. Gadolinium neutron capture therapy (GdNCT) is binary radiotherapy based on a localized nuclear reaction that produces high-energy radiations (e.g., Auger electrons, gamma-rays, etc.) in cancer cells when 157Gd is irradiated with thermal neutrons. Yet, its clinical application has been postponed due to the poor ability of Auger electrons and gamma-rays to kill cells. Here, we engineered a 157Gd-porphyrin framework that synergizes GdNCT and dynamic therapy to efficiently produce both center dot OH and immunogenic 1O2 in cancer cells, thereby provoking a strong antitumor immune response. This study unveils the fact and mechanism that NDT heats tumor immunity. Another unexpected finding is that the Auger electron can be the most effective energy-transfer medium for radiation-induced activation of nanomedicines because its nanoscale trajectory perfectly matches the size of nanomaterials. In mouse tumor models, NDT causes nearly complete regression of both primary and distant tumor grafts. Thus, this 157Gd-porphyrin framework radioenhancer endows GdNCT with the exotic function of triggering dynamic therapy; its application may expand in clinics as a new radiotherapy modality that utilizes GdNCT to provoke whole-body antitumor immune response for treating metastases, which are responsible for 90% of all cancer deaths.