Dancy, Jimena G.

DART nanoparticles overcome critical drug delivery barriers for primary tumors and brain metastases.

Glioblastoma (GBM) is a highly aggressive and lethal form of primary brain cancer. Numerous barriers exist to the effective treatment ofGBMincluding the tightly controlled interface between the bloodstream and central nervous system termed the ‘neurovascular unit,’ a narrow and tortuous tumor extracellular space containing a dense meshwork of proteins and glycosaminoglycans, and genomic heterogeneity and instability. A major goal ofGBMtherapy is achieving sustained drug delivery to glioma cells while minimizing toxicity to adjacent neurons and glia. Targeted nanotherapeutics have emerged as promising drug delivery systems with the potential to improve pharmacokinetic profiles and therapeutic efficacy. Some of the key cell surface molecules that have been identified asGBMtargets include the transferrin receptor, low‐density lipoprotein receptor‐related protein, αvβ3integrin, glucose transporter(s), glial fibrillary acidic protein, connexin 43, epidermal growth factor receptor (EGFR),EGFRvariantIII, interleukin‐13 receptor α chain variant 2, and fibroblast growth factor‐inducible factor 14. However, most targeted therapeutic formulations have yet to demonstrate improved efficacy related to disease progression or survival. Potential limitations to current targeted nanotherapeutics include: (1) adhesive interactions with nontarget structures, (2) low density or prevalence of the target, (3) lack of target specificity, and (4) genetic instability resulting in alterations of either the target itself or its expression level in response to treatment. In this review, we address these potential limitations in the context of the keyGBMtargets with the goal of advancing the understanding and development of targeted nanotherapeutics forGBM.WIREs Nanomed Nanobiotechnol2017, 9:e1439. doi: 10.1002/wnan.1439This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging TechnologiesTherapeutic Approaches and Drug Discovery > Nanomedicine for Neurological DiseaseTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease