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Drug-loaded nanoparticles induce immunogenic cell death and efficiently target cells from glioblastoma patients

Title: Drug-loaded nanoparticles induce immunogenic cell death and efficiently target cells from glioblastoma patients
Authors: 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
Contributors: 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
Publisher Information: Taylor & Francis
Publication Year: 2025
Collection: Padua Research Archive (IRIS - Università degli Studi di Padova)
Subject Terms: Immunogenic cell death; U87MG; damage-associated molecular pattern; diaminocyclohexane-platinum II (DACHPt); glioblastoma; oxaliplatin; polymeric nanoparticle; tumor microenvironment
Description: 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.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/40326623; info:eu-repo/semantics/altIdentifier/wos/WOS:001482581500001; firstpage:1; lastpage:12; numberofpages:12; journal:NANOMEDICINE; https://hdl.handle.net/11577/3552910
DOI: 10.1080/17435889.2025.2497747
Availability: https://hdl.handle.net/11577/3552910; https://doi.org/10.1080/17435889.2025.2497747
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.27FD6539
Database: BASE