title: Nanoparticles for Targeting Intratumoral Hypoxia: Exploiting a Potential Weakness of Glioblastoma.
abstract: Extensive hypoxic regions are the daunting hallmark of glioblastoma, as they host aggressive stem-like cells, hinder drug delivery and shield cancer cells from the effects of radiotherapy. Nanotechnology could address most of these issues, as it employs nanoparticles (NPs) carrying drugs that selectively accumulate and achieve controlled drug release in tumor tissues. Methods overcoming the stiff interstitium and scarce vascularity within hypoxic zones include the incorporation of collagenases to degrade the collagen-rich tumor extracellular matrix, the use of multistage systems that progressively reduce NP size or of NP-loaded cells that display inherent hypoxia-targeting abilities. The unfavorable hypoxia-induced low pH could be converted into a therapeutical advantage by pH-responsive NPs or multilayer NPs, while overexpressed markers of hypoxic cells could be specifically targeted for an enhanced preferential drug delivery. Finally, promising new gene therapeutics could also be incorporated into nanovehicles, which could lead to silencing of hypoxia-specific genes that are overexpressed in cancer cells. In this review, we highlight NPs which have shown promising results in targeting cancer hypoxia and we discuss their applicability in glioblastoma, as well as possible limitations. Novel research directions in this field are also considered.
authors.affiliation: Department of Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes Str, Cluj-Napoca, Romania, 400012. mihaela.aldea1@gmail.com.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Aldea
authors.affiliation: Department of Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. florian.ioan.alexandru@gmail.com.
authors.forename: Ioan Alexandru
authors.initials: IA
authors.lastname: Florian
authors.affiliation: Department of Oncology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Victor Babes Str, Cluj-Napoca, Romania, 400012.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kacso
authors.affiliation: Department of Pathology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Lucian
authors.initials: L
authors.lastname: Craciun
authors.affiliation: Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute on Bio-Nano-Sciences, Babes-Bolyai University, Cluj-Napoca, Romania.
authors.forename: Sanda
authors.initials: S
authors.lastname: Boca
authors.affiliation: Department of Tumor Biology, Ion Chiricuta Cancer Center, Cluj-Napoca, Romania.
authors.forename: Olga
authors.initials: O
authors.lastname: Soritau
authors.affiliation: Department of Neurosurgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
authors.forename: Ioan Stefan
authors.initials: IS
authors.lastname: Florian
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D053758:Nanoparticles / Q000008:administration & dosage*
chemical_list: D003692:Delayed-Action Preparations
keywords: glioblastoma; hypoxia; nanoparticles