Self-Immunomodulatory Nanoparticles for the Locoregional Treatment of Glioblastoma

Serena Zilio – Senior Medical Researcher, Veneto Institute of Oncology, IOV–IRCCS; Weisha Qi – Laboratory Technician, Veneto Institute of Oncology, IOV–IRCCS; Sofia Banzato – Student, Department of Pharmaceutical and Pharmacological Sciences, University of Padova; Mariangela Garofalo – Associate Professor, Department of Pharmaceutical and Pharmacological Sciences, University of Padova; Ilaria Marigo – Associate Professor, Veneto Institute of Oncology, IOV–IRCCS; Stefefano Salmaso – Full Professor, Department of Pharmaceutical and Pharmacological Sciences, University of Padova; Paolo Caliceti – Full Professor, Department of Pharmaceutical and Pharmacological Sciences, University of Padova; Alessio Malfanti – Associate Professor, Department of Pharmaceutical and Pharmacological Sciences, University of Padova

Introduction:

Glioblastoma (GBM) is the most common primary brain tumor. Challenges in GBM treatment are associated with a highly immunosuppressive tumor immune microenvironment (TIME) enriched in M2-like tumor-associated macrophages¹. We designed a class of nanoparticles (NPs) based on crosslinked hyaluronic acid (HA) and poly-L-lysine (PL) with intrinsic immunomodulatory capacity, for GBM local drug delivery. The use of 100 kDa HA is related to immunomodulatory activity via CD44 and Toll-like receptors 2/4, while PL enhances brain parenchyma penetration, further potentiating HA immunological effects².

Learning Objectives:

• To design self-immunomodulatory nanoparticles for the local treatment of GBM.
• To evaluate the immunomodulatory effects of HAPL nanoparticles in an immune-refractory glioblastoma model.