X-ray-Activated Nanoneutrophils for Orthotopic Glioma Immunotherapy

Emerging cell-mimetic nanodevices have provided promising strategies for solid tumor treatment, yet their therapeutic efficacy and specificity remain very limited. Inspired by the characteristics of natural neutrophils, we developed a semiconducting polymer-based artificial nanoneutrophil with X-ray-responsive activity for orthotopic glioma therapy. This nanoneutrophil with neutrophil membrane camouflage could cross the blood-brain barrier and achieve enhanced infiltration into orthotopic glioma. Moreover, this nanoneutrophil enabled X-ray-activatable release of elastase to kill tumor cells via a neutrophil-mimetic manner. X-ray-activated nanoneutrophils could also induce immunogenic cell death to amplify the systemic immune effect for eliminating orthotopic glioma. This strategy enabled specific and highly efficient therapy of orthotopic glioma in immunodeficient nude mouse models via neutrophil-mimetic therapeutic action, as well as in normal mouse models by inducing an adaptive T-cell response. This nanoneutrophil presents a distinct paradigm of cell-mimetic nanodevices with X-ray-responsive activity for deep tissue-seated cancer therapy.