Tumor-targeted nanotherapeutics: Overcoming treatment barriers for glioblastoma

Aniket S. Wadajkar, Jimena G. Dancy, David S. Hersh, Pavlos Anastasiadis, Nhan Tran, Graeme F. Woodworth, Jeffrey A. Winkles, Anthony J. Kim

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Glioblastoma (GBM) is a highly aggressive and lethal form of primary brain cancer. Numerous barriers exist to the effective treatment of GBM including 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 of GBM therapy 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 as GBM targets include the transferrin receptor, low-density lipoprotein receptor-related protein, αvβ3 integrin, glucose transporter(s), glial fibrillary acidic protein, connexin 43, epidermal growth factor receptor (EGFR), EGFR variant III, 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 key GBM targets with the goal of advancing the understanding and development of targeted nanotherapeutics for GBM. For further resources related to this article, please visit the WIREs website.

Original languageEnglish (US)
JournalWiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology
DOIs
StateAccepted/In press - 2016

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Bioengineering
  • Biomedical Engineering

Cite this

Wadajkar, A. S., Dancy, J. G., Hersh, D. S., Anastasiadis, P., Tran, N., Woodworth, G. F., Winkles, J. A., & Kim, A. J. (Accepted/In press). Tumor-targeted nanotherapeutics: Overcoming treatment barriers for glioblastoma. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. https://doi.org/10.1002/wnan.1439