Ultrasound-responsive nutlin-loaded nanoparticles for combined chemotherapy and piezoelectric treatment of glioblastoma cells

• DOI: 10.1016/j.actbio.2021.04.005
• Publication Date: 2021-04-21T09:03:19Z
• Authors: Carlotta Pucci; Attilio Marino; Özlem Şen; Daniele De Pasquale; Martina Bartolucci; Nerea Iturrioz-Ro...; Nicoletta di Leo; Giuseppe de Vito; Doriana Debellis; Andrea Petretto; Gianni Ciofani
• Keywords: Temozolomide; PLGA

Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, represents the most aggressive primary brain tumor. The complex genetic heterogeneity, acquired drug resistance, and presence of blood-brain barrier (BBB) limit efficacy current therapies, with effectiveness demonstrated only in a small subset patients. To overcome these issues, here we propose an anticancer approach based on ultrasound-responsive drug-loaded organic piezoelectric nanoparticles. This nanoplatform consists nutlin-3a-loaded ApoE-functionalized P(VDF-TrFE) nanoparticles, that can be remotely activated ultrasound-based mechanical stimulations to induce release locally deliver electric cues. combination chemotherapy treatment chronic stimulation resulted activation cell apoptosis anti-proliferation pathways, induction necrosis, inhibition cancer migration, reduction invasiveness drug-resistant GBM cells. Obtained results pave way for use innovative multifunctional nanomaterials less invasive more focused treatments, able reduce resistance GBM. STATEMENT OF SIGNIFICANCE: Piezoelectric hybrid lipid-polymeric efficiently encapsulating non-genotoxic (nutlin-3a) functionalized peptide (ApoE) enhances their passage through BBB, are proposed. Upon ultrasound stimulation, nanovectors actin polymerization, invasion ability glioma cells, while fostering apoptotic necrotic events. wireless action paves invasive, efficient therapeutic strategy.