Nanodrug constructed using dietary antioxidants for immunotherapy of metastatic tumors

Immunogenic cell death (ICD) induced by reactive oxygen species (ROS) represents a particular form of tumor cell death for approaching the problem of low immunogenicity of tumors in immunotherapy, while the oxidative damage to normal cells of current ICD inducers hinders their clinical application. Herein, a new ICD inducer VC@cLAV constructed solely by dietary antioxidants, lipoic acid (LA) and vitamin C (VC), is developed, which could promote heavy intracellular ROS production in cancer cells for ICD induction while acting as an anti-oxidant in non-cancer cells for cytoprotection, and thus hold high biosafety. In vitro studies show that VC@cLAV induced a release of antigens and a maturation rate of DCs up to 56.5%, approaching the positive control (58.4%). In vivo combined with alpha PD-1, VC@cLAV showed excellent antitumor activity against both primary and distant metastatic tumors with an inhibition rate of 84.8% and 79.0% compared to 14.2% and 10.0% in the alpha PD-1 alone group. Notably, VC@cLAV established a long-term antitumor immune memory effect against tumor rechallenging. This study not only presents a new kind of ICD inducer but also provides an impetus for the development of dietary antioxidant-based cancer drugs.

Automated summary

A new immunogenic cell death (ICD) inducer, VC@cLAV, constructed by dietary antioxidants, lipoic acid (LA) and vitamin C (VC), shows potential as a safe and effective treatment for tumors. It induces high levels of reactive oxygen species (ROS) in cancer cells for ICD induction, while acting as an antioxidant in normal cells for cytoprotection. In preclinical studies, VC@cLAV demonstrates excellent antitumor activity and long-term immune memory effects.