Nanomedicine-mediated programmed necrosis for cancer immunosurveillance

The cancer-immunity cycle begins with the death of cancer cells, making the mode of cell death a critical determinant of antitumor immune responses. Apoptosis, the predominant form of cell death in most tumors, is often immunologically silent and therefore provides limited support for effective antitumor immunity. By contrast, programmed necrosis promotes cancer immunosurveillance through membrane disruption and the release of immunostimulatory intracellular contents and inflammatory mediators that facilitate immune priming. However, therapeutic induction of these pathways remains challenging, as many cancers harbour molecular defence mechanisms that impair their execution, while tumor heterogeneity, immunosuppressive microenvironments and biological barriers further constrain therapeutic efficacy. In this context, nanomedicine offers a promising strategy for overcoming these limitations by enhancing tumor accumulation through the rational design of physicochemical properties. This Review discusses the immunological significance of programmed necrosis, with particular emphasis on the biological contexts governing its induction, and highlights recent advances in nanomedicines designed to trigger these pathways, including their mechanisms of action, translational challenges and future prospects for cancer immunotherapy.