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Long Circulation and Tumor Accumulation

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Cancer Targeted Drug Delivery

Abstract

Nanoparticles have been employed in cancer management as vectors to deliver chemotherapeutic and/or imaging agents to tumors. Enhanced tumor accumulation occurs by virtue of the long circulation properties of the nanocarrier and the enhanced permeability and retention effect that is characteristic of solid tumors. The versatility of the nanoparticle platform has enabled the design and development of various nanocarriers differing in physicochemical properties such as surface composition, size, charge, and shape. While such properties can influence the pharmacokinetics and biodistribution of a formulation, total tumor deposition can be further impacted by inherent pathophysiology of the tissue. This chapter presents the nature and impact of nanoparticle design on tumor accumulation, particularly in the context of the tumor microenvironment. In vivo barriers, such as opsonization, impaired tumor blood flow, heterogeneous vascular and interstitial permeability impede the effective delivery of nanocarriers and their cargo and are discussed herein, while strategies to overcome them and enhance the effective delivery of nanoparticles are presented.

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Acknowledgments

This work was supported by a grant from the Canadian Institutes of Health Research (CIHR) to C.A., and D.A.J. S.N.E is supported by a fellowship from the CIHR Strategic Training Program in Biological Therapeutics.

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Authors and Affiliations

  1. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada

    Sandra N. Ekdawi, Andrew S. Mikhail, Sina Eetezadi & Christine Allen Ph.D.

  2. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada

    Andrew S. Mikhail, David A. Jaffray Ph.D. & Christine Allen Ph.D.

  3. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Shawn Stapleton & David A. Jaffray Ph.D.

  4. STTARR Innovation Centre, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

    Shawn Stapleton, Jinzi Zheng Ph.D., David A. Jaffray Ph.D. & Christine Allen Ph.D.

  5. Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada

    David A. Jaffray Ph.D.

  6. Radiation Physics Department, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

    David A. Jaffray Ph.D.

  7. Techna Institute and Ontario Cancer Institute, University Health Network, Toronto, ON, Canada

    David A. Jaffray Ph.D.

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  1. Sandra N. Ekdawi
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  2. Andrew S. Mikhail
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  4. Jinzi Zheng Ph.D.
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  5. Sina Eetezadi
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  6. David A. Jaffray Ph.D.
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  7. Christine Allen Ph.D.
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Correspondence to Christine Allen 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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Ekdawi, S.N. et al. (2013). Long Circulation and Tumor Accumulation. 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_20

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