Porphyrin-Engineered 125I-Nanoseeds as a Prototype for Immunogenic Brachytherapy

Internal radiotherapy holds a greater potential than external radiotherapy for precisely destroying tumors and minimizing side effects. 125I seeds are routinely used as radioactive sources in clinical brachytherapy for patients with various types of cancers. However, 125I seeds are losing ground to flashier cancer therapies, mainly due to their limited therapeutic efficacy, uneven dose distribution, and negligible antitumor immune response. Here, we present porphyrin-engineered 125I-nanoseeds as a prototype for immunogenic brachytherapy. 125I-nanoseeds were rationally designed as a core-shell structure, in which Au@Ag cores enhance the energy deposition of photons to produce more ·OH, while porphyrin shells transfer the energy of Auger electrons to generate 1O2. Benefiting from improving energy utilization efficiency, 125I-nanoseeds can efficiently produce ·OH and 1O2 in tumors, enhancing antitumor efficacy and inducing immunogenic cell death in both murine tumor models and human tumor tissues. When combined with checkpoint blockade immunotherapy, 125I-nanoseeds elicit a systemic immune response in tumor-bearing mice, inhibiting both distant and metastatic tumors. This work demonstrates that porphyrin-engineered 125I-nanoseeds can synergize brachytherapy and dynamic therapy, resulting in enhanced antitumor efficacy and antitumor immune response compared to those of clinical 125I seeds, which is expected to improve the applied prospect of clinical brachytherapy.