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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: Ada Tushe; Elena Marinelli; Beatrice Musca; Annavera Ventura; Sara Zumerle; Olga Slukinova; Giulia Zampardi; Francesco Volpin; Camilla Bonaudo; Alessandro Della Puppa; Mathieu Repellin; Giulia Guerriero; Giovanna Lollo; Susanna Mandruzzato
Publication Year: 2025
Subject Terms: Biophysics; Cell Biology; Pharmacology; Biotechnology; Immunology; Cancer; Space Science; Biological Sciences not elsewhere classified; Chemical Sciences not elsewhere classified; Immunogenic cell death; polymeric nanoparticles; diaminocyclohexane-platinum II (DACHPt); damage-associated molecular patterns; oxaliplatin; U87MG; tumor microenvironment; glioblastoma
Description: 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. 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). 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. 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: dataset
Language: unknown
DOI: 10.6084/m9.figshare.28937754.v1
Availability: https://doi.org/10.6084/m9.figshare.28937754.v1; https://figshare.com/articles/dataset/Drug-loaded_nanoparticles_induce_immunogenic_cell_death_and_efficiently_target_cells_from_glioblastoma_patients/28937754
Rights: CC BY 4.0
Accession Number: edsbas.764E7C08
Database: BASE