Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles.
Glioblastoma multiforme (GBM) are extremely lethal and still poorly treated primary brain tumors, characterized by the presence of highly tumorigenic cancer stem cell (CSC) subpopulations, considered responsible for tumor relapse. In order to successfully eradicate GBM growth and recurrence, new anti-cancer strategies selectively targeting CSCs should be designed. CSCs might be eradicated by targeting some of their cell surface markers and transporters, inducing their differentiation, impacting their hyper-glycolytic metabolism, inhibiting CSC-related signaling pathways and/or by targeting their microenvironmental niche. In this regard, phytocompounds such as curcumin, isothiocyanates, resveratrol and epigallocatechin-3-gallate have been shown to prevent or reverse cancer-related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemotherapy and radiotherapy efficacy. However, the actual bioavailability and metabolic processing of phytocompounds is generally unknown, and the presence of the blood brain barrier often represents a limitation to glioma treatments. Nowadays, nanoparticles (NPs) can be loaded with therapeutic compounds such as phytochemicals, improving their bioavailability and their targeted delivery within the GBM tumor bulk. Moreover, NPs can be designed to increase their tropism and specificity toward CSCs by conjugating their surface with antibodies specific for CSC antigens, with ligands or with glucose analogues. Here we discuss the use of phytochemicals as anti-glioma agents and the applicability of phytochemical-loaded NPs as drug delivery systems to target GBM. Additionally, we provide some examples on how NPs can be specifically formulated to improve CSC targeting.
Oncohematology Laboratory, Department of Woman and Child Health, University of Padova, Padova, Italy.|Centre for Nutrition and Health, Universidad Europea del Atlántico (UEA), Santander, Spain.
Francesca
F
Pistollato
Nanobioscience Unit, Institute for Health and Consumer Protection (IHCP), Joint Research Centre (JRC) - European Commission, Ispra, Varese, Italy.
Susanne
S
Bremer-Hoffmann
Oncohematology Laboratory, Department of Woman and Child Health, University of Padova, Padova, Italy.
Giuseppe
G
Basso
Centre for Nutrition and Health, Universidad Europea del Atlántico (UEA), Santander, Spain.|Universidad Internacional Iberoamericana (UNINI), Campeche, Mexico.|Fundación Universitaria Iberoamericana, (FUNIBER), Barcelona, Spain.
Sandra Sumalla
SS
Cano
Centre for Nutrition and Health, Universidad Europea del Atlántico (UEA), Santander, Spain.|Universidad Internacional Iberoamericana (UNINI), Campeche, Mexico.|Fundación Universitaria Iberoamericana, (FUNIBER), Barcelona, Spain.
Iñaki
I
Elio
Centre for Nutrition and Health, Universidad Europea del Atlántico (UEA), Santander, Spain.|Universidad Internacional Iberoamericana (UNINI), San Juan, PR, USA.
Manuel Masias
MM
Vergara
Centre for Nutrition and Health, Universidad Europea del Atlántico (UEA), Santander, Spain. f.giampieri@univpm.it.|Dipartimento di Scienze Agrarie, Alimentari ed Ambientali (D3A), Università Politecnica delle Marche, Ancona, Italy. f.giampieri@univpm.it.
Francesca
F
Giampieri
Centre for Nutrition and Health, Universidad Europea del Atlántico (UEA), Santander, Spain. m.a.battino@univpm.it.|Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona, Italy. m.a.battino@univpm.it.
Maurizio
M
Battino
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D064209:Phytochemicals / Q000627:therapeutic use*; D008517:Phytotherapy
D064209:Phytochemicals