Hamayesh Arwin Alborz همایش آروین البرز MHHJR فصلنامه پژوهش‌های نوین در علوم پزشکی، بهداشت و سلامت | MHHJR 2 4 2026 10 12 Engineering a Neutrophil-Mimetic AIEgen/CRISPR Nanoplatform for CD73 Ablation and Photo-Immunotherapy Remodeling in Glioblastoma Engineering a Neutrophil-Mimetic AIEgen/CRISPR Nanoplatform for CD73 Ablation and Photo-Immunotherapy Remodeling in Glioblastoma 36 55 FA Mohammad Sadegh Khalaj - B.Sc. in Animal Science, Department of Animal Science, Faculty of Biological Sciences, Kharazmi University (Tehran), Alborz Campus Mohammad Sadegh Khalaj - B.Sc. in Animal Science, Department of Animal Science, Faculty of Biological Sciences, Kharazmi University (Tehran), Alborz Campus 2026 09 23 Glioblastoma (GBM) is the deadliest primary brain tumour with an immunosuppressive TME and multiple mechanisms for treatment resistance. The adenosine pathway mediated by ecto-enzyme CD73 plays an important role in tumor progression and immunoescape. In this work, a novel biomimetic nanoplatform with multiple functions was designed for the co-treatment of GBM. This new approach, Neu-AMC, consists of a novel nanocarrier by loading CRISPR/Cas9 complex of NT5E (encoding CD73) gene and aggregation-induced emission luminogen (AIEgen) photosensitizer into neutrophil membrane-cloaked nanoparticles for working on the blood-brain barrier (BBB) crossing and tumour targeting properties of neutrophils. The nanoplatform was validated to have outstanding efficiency on crossing an in vitro BBB model and actively targeting GBM. When accumulated into tumour tissues, the CRISPR/Cas9 genome-editing system exhibited a highly specific and efficient knockout of CD73 with remarkable depletion of immunosuppressive adenosine, while NIR light irradiation of the AIEgen for photoexciting a burst of reactive oxygen species (ROS) that can directly induce photodynamic therapy (PDT) along with immunogenic cell death (ICD) effectively remodel the TME, dramatically depleting the M2-like macrophages and myeloid-derived suppressor cells (MDSCs), and augmenting the infiltration and cytotoxic effects of CD8+ T cells and NK cells. An orthotopic GBM mouse model demonstrated that the combination of Neu-AMC treatment with NIR irradiation can cause near-complete tumor remission and prolonged survival and long-term memory effects. Our study provides a powerful and adaptive strategy based on precise gene editing and photo-immunotherapy to treat GBM. Glioblastoma (GBM) is the deadliest primary brain tumour with an immunosuppressive TME and multiple mechanisms for treatment resistance. The adenosine pathway mediated by ecto-enzyme CD73 plays an important role in tumor progression and immunoescape. In this work, a novel biomimetic nanoplatform with multiple functions was designed for the co-treatment of GBM. This new approach, Neu-AMC, consists of a novel nanocarrier by loading CRISPR/Cas9 complex of NT5E (encoding CD73) gene and aggregation-induced emission luminogen (AIEgen) photosensitizer into neutrophil membrane-cloaked nanoparticles for working on the blood-brain barrier (BBB) crossing and tumour targeting properties of neutrophils. The nanoplatform was validated to have outstanding efficiency on crossing an in vitro BBB model and actively targeting GBM. When accumulated into tumour tissues, the CRISPR/Cas9 genome-editing system exhibited a highly specific and efficient knockout of CD73 with remarkable depletion of immunosuppressive adenosine, while NIR light irradiation of the AIEgen for photoexciting a burst of reactive oxygen species (ROS) that can directly induce photodynamic therapy (PDT) along with immunogenic cell death (ICD) effectively remodel the TME, dramatically depleting the M2-like macrophages and myeloid-derived suppressor cells (MDSCs), and augmenting the infiltration and cytotoxic effects of CD8+ T cells and NK cells. An orthotopic GBM mouse model demonstrated that the combination of Neu-AMC treatment with NIR irradiation can cause near-complete tumor remission and prolonged survival and long-term memory effects. Our study provides a powerful and adaptive strategy based on precise gene editing and photo-immunotherapy to treat GBM. https://mhhjr.ir/downloadfilepdf/11965