Nanomedicine (London, England) · 2025
Drug-loaded nanoparticles induce immunogenic cell death and efficiently target cells from glioblastoma patients.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Tushe Ada, Marinelli Elena, Musca Beatrice, Ventura Annavera, Zumerle Sara, Slukinova Olga, Zampardi Giulia, Volpin Francesco, Bonaudo Camilla, Della Puppa Alessandro, Repellin Mathieu, Guerriero Giulia, Lollo Giovanna, Mandruzzato Susanna
Аннотация
AIM: Glioblastoma multiforme (GBM) is characterized by a highly immunosuppressive tumor microenvironment (TME), posing significant challenges for efficient therapy's outcomes. Nanomedicine combined with immunotherapy holds the potential to modulate the TME and reactivate immune responses. This study proposes a polymeric nanosystem (NPs) encapsulating diaminocyclohexane-platinum II (DACHPt), an oxaliplatin derivative, to induce immunogenic cell death (ICD) in GBM cells.
MATERIALS & METHODS: An ionic-gelation technique was employed to generate polymeric nanoparticles (NPs) with an approximate size of 200 nm. NPs internalization was analyzed in GBM cell lines, in vitro-derived macrophages, and in leukocytes and tumor cells from GBM patient via flow cytometry and confocal imaging. ICD was assessed by measuring two of its main markers: adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1).
RESULTS: NPs were efficiently incorporated by myeloid and tumor cells, but not by lymphocytes. DACHPt-loaded NPs demonstrated enhanced cytotoxicity compared to free drug, with increased ATP and HMGB1 release from GBM cells, confirming ICD induction.
CONCLUSIONS: Our findings suggest that DACHPt-loaded NPs represent a promising therapeutic strategy capable of targeting both tumor cells and tumor-promoting immune cells while inducing ICD.
MATERIALS & METHODS: An ionic-gelation technique was employed to generate polymeric nanoparticles (NPs) with an approximate size of 200 nm. NPs internalization was analyzed in GBM cell lines, in vitro-derived macrophages, and in leukocytes and tumor cells from GBM patient via flow cytometry and confocal imaging. ICD was assessed by measuring two of its main markers: adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1).
RESULTS: NPs were efficiently incorporated by myeloid and tumor cells, but not by lymphocytes. DACHPt-loaded NPs demonstrated enhanced cytotoxicity compared to free drug, with increased ATP and HMGB1 release from GBM cells, confirming ICD induction.
CONCLUSIONS: Our findings suggest that DACHPt-loaded NPs represent a promising therapeutic strategy capable of targeting both tumor cells and tumor-promoting immune cells while inducing ICD.