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Tumor Vasculature, EPR Effect, and Anticancer Nanomedicine: Connecting the Dots

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Cancer Targeted Drug Delivery

Abstract

The progression of a tumor cell mass beyond 2 mm is critically dependent on neoangiogenesis. Angiogenic factors secreted by tumor cells, infiltrating macrophages, and stromal cells aggressively promote proliferation and migration of endothelial cells. The nascent primitive vasculatures are usually morphologically and functionally abnormal due to several features such as the lack of a vascular smooth muscle cell layer, abrupt change of the blood vessel diameter, tortuosity, and leakiness. Those characteristics which alter the blood flow and the transport of molecules in tumors led to the discovery of the enhanced permeability and retention (EPR) of nanosize molecules in tumor tissues. Following its discovery, various anticancer nanoconstructs have been developed with the EPR effect as a central mechanism for tumor targeting. However, the development of these nanodrugs has been hampered by a slow progress towards the clinic. Only nine nanomedicines have been approved for anticancer treatment for the last 26 years. In this chapter, we discuss various aspects that may explain the limited transition for an efficient anticancer nanomedicine. The specificity of the tumor vasculature, the discrepancy in tumor biology, the role of animal tumor models, and the physicochemical characteristics of nanoconstructs are closely examined. This chapter provides new considerations for successful development of EPR-based anticancer nanomedicine.

Sebastien Taurin and Hayley Nehoff contributed equally to the work.

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Abbreviations

EPR:

Enhanced permeability and retention

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

bFGF:

Basic fibroblast growth factor

TGF:

Tumor growth factor

MMP:

Matrix metalloproteinases

NO:

Nitric oxide

EBD:

Evans blue dye

SMANCS:

Styrene co-maleic acid conjugated neocarzinostatin

TDT:

Tumor doubling time

HPMA:

N-(2-hydroxypropyl)methacrylamide

RES:

Reticuloendothelial system

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand

    Sebastien Taurin, Hayley Nehoff, Thalita van Aswegen & Khaled Greish M.D., Ph.D

  2. Department of Oncology, Faculty of Medicine, Suez Canal University, Suez, Egypt

    Khaled Greish M.D., Ph.D

Authors
  1. Sebastien Taurin
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  2. Hayley Nehoff
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  3. Thalita van Aswegen
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  4. Khaled Greish M.D., Ph.D
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Correspondence to Khaled Greish M.D., Ph.D .

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Editors and Affiliations

  1. Pharmacutics & Pharmacutical Chemistry, University of Utah, Salt Lake City, Utah, USA

    You Han Bae

  2. Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom

    Randall J. Mrsny

  3. Department of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA

    Kinam Park

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Taurin, S., Nehoff, H., van Aswegen, T., Greish, K. (2013). Tumor Vasculature, EPR Effect, and Anticancer Nanomedicine: Connecting the Dots. In: Bae, Y., Mrsny, R., Park, K. (eds) Cancer Targeted Drug Delivery. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7876-8_8

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