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Glioblastoma multiforme selective nanomedicines for improved anti-cancer treatments

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posted on 2023-04-06, 09:34 authored by Jason Thomas Duskey, Arianna Rinaldi, Ilaria Ottonelli, Riccardo Caraff, Chiara DeBenedictisChiara DeBenedictis, Ann Katrin SauerAnn Katrin Sauer, Giovanni Tosi, Maria Angela Vandelli, Barbara Ruozi, Andreas GrabruckerAndreas Grabrucker

Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines (NMeds) offer a way to overcome these pitfalls by protecting and loading drugs, increasing blood half-life, and being targetable with specific ligands on their surface. In this study, the FDA-approved polymer poly (lactic-co-glycolic) acid was used to optimise NMeds that were surface modified with a series of potential GBM-specific ligands. The NMeds were fully characterised for their physical and chemical properties, and then in vitro testing was performed to evaluate cell uptake and GBM cell specificity. While all targeted NMeds showed improved uptake, only those decorated with the-cell surface vimentin antibody M08 showed specificity for GBM over healthy cells. Finally, the most promising targeted NMed candidate was loaded with the well-known chemotherapeutic, paclitaxel, to confirm targeting and therapeutic effects in C6 GBM cells. These results demonstrate the importance of using well-optimised NMeds targeted with novel ligands to advance delivery and pharmaceutical effects against diseased cells while minimising the risk for nearby healthy cells.

Funding

Investigating Mechanisms and Models Predictive of Accessibility of Therapeutics (IM2PACT) Into The Brain

European Commission

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History

Publication

Pharmaceutics 2022, 14, 1450

Publisher

MDPI

Other Funding information

This research was partially funded by an IMI EU Grant “Investigating Mechanisms and Models predictive of accessibility of therapeutics (IM2PACT) Into the Brain” IMI2—Call 12, GA n.807015 (im2pact.org); FAR Unimore Fondazione di Modena “Nano-immuno targeting per il trattamento del glioblastoma multiforme” NIT Project; GLIOSILK Project (Reference Number: EURONANOMED2019-075); a Ministero degli Esteri e della Cooperazione Internazionale MAECI grant, Progetti di ricerca scientifica e tecnologica di grande rilevanza by Ministero degli Esteri, Progetti Italy-USA, “Nanomedicine for Blood Brain Barrier (BBB)-crossing in CNS oncologic pathologies”, Prot. nr. MAE00691612020-06-26; The University of Limerick Cancer Network (ULCaN) Pilot Project Scheme 2020; Project title: Improved Brain-Targeted Anti-GBM Nanoparticles. Creutzfeldt–Jakob disease Foundation (CJDF); Telethon GGP19113 project: “Pigment Epithelium-derived Factor (PEDF) peptide as therapeutic agents for inherited retinal degeneration

Also affiliated with

  • Bernal Institute
  • Health Research Institute (HRI)

Department or School

  • Biological Sciences

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