System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Research Support, Non-U.S. Gov't Ppublish

PubMed: 40326623 DOI: 10.1080/17435889.2025.2497747

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

Nanomedicine (Lond) 20(11):1223-1234

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

Affiliations

  • Veneto Institute of Oncology IOV, IRCCS, Padua, Italy.
  • Department of Surgery, Oncology and Gastroneterology, University of Padua, Padua, Italy.
  • Division of Neurosurgery, University Hospital of Padova, Padova, Italy.
  • Neurosurgery, Department of NEUROFARBA, University of Florence, University Hospital of Careggi, Florence, Italy.
  • Laboratoire D'Automatique, de Génie des Procédés et de Génie Pharmaceutique, LAGEPP UMR 5007, University Lyon 1, CNRS, Lyon, France.
  • Institut universitaire de France (IUF), Paris, France.

Abstract

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.

MeSH

Cells, Nanomedicine, Nanoparticles, Pharmaceutical Preparations, Neoplasms, Immunogenic Cell Death, Oxaliplatin, Glioblastoma, Cell Death, Tumor Microenvironment