OS10.4.A A macrophage-based drug delivery platform for glioma treatment
نویسندگان
چکیده
Abstract Background There is an urgent need for more effective treatment strategies against gliomas. At present, even though various drugs have potent anti-tumor activity in vitro, their application vivo limited by ineffective delivery and systemic toxicity. Therefore, novel are needed to deliver these effectively safely the tumor site. Here, we developed adoptive transfer strategy malignant brain tumors utilizing macrophages that loaded with ferritin-protein cages containing or other proteins nanocarriers cancer cells vitro vivo. Material Methods Live-time imaging, microscopy flow cytometry were utilized investigate of ferritin from human mouse glioma cells. Co-cultures ferritin-drug used study anti-glioma orthotopic immunocompetent models Affinity purification-mass spectrometry (AP-MS) was elucidate mechanisms characterizing interactome within Results We observed a high efficiency ferritin-cages into co-culture assays confirmed also upon intravenous intratumoral GL-261 CT-2A glioma-bearing mice. To therapeutically active payloads, murine/human carrying cytotoxic payloads. Co-culture murine revealed time- concentration-dependent cytotoxicity In vivo, administration protein tolerated without toxicities conferred survival benefit two (GL-261 CT-2A). Interactome studies ferritin-cage-binding phagocytic cytoskeleton re-arrangement pathways be involved uptake Conclusion This ‘Trojan Horse’ approach constitutes promising platform gliomas provides rationale clinical translation.
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ژورنال
عنوان ژورنال: Neuro-oncology
سال: 2022
ISSN: ['1523-5866', '1522-8517']
DOI: https://doi.org/10.1093/neuonc/noac174.067