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Cancer Chemotherapy

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Fundamentals of Pharmaceutical Nanoscience

Abstract

The enhanced permeability and retention (EPR) effect is the first essential step for selective delivery of macromolecular drugs to tumor tissues. The EPR effect is based on the aberrant architecture of tumor blood vessels and the impaired lymphatic drainage system in tumor tissue. This effect is facilitated by overproduction of multiple vascular mediators such as bradykinin, nitric oxide, prostaglandins, vascular endothelial growth factor (VEGF), and other cytokines in tumor tissue, which may also affect surrounding normal tissues. The biocompatibility, molecular size, and surface charge of macromolecular drugs, i.e., nanomedicines, are critical determinants of tumor-targeted drug delivery based on the EPR effect. However, ineffective treatment can result from the heterogeneity of the EPR effect in tumor tissues, which impedes drug delivery to some tumors. In this chapter, we also discuss how to overcome this problem by using specific therapeutic methods, such as angiotensin (AT) II-induced high blood pressure, angiotensin-converting enzyme inhibitors, nitric oxide-releasing agents, tumor necrosis factor-α, transforming growth factor-β, and heme oxygenase-1 inducer, some of which were demonstrated to be effective in clinical settings.

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Abbreviations

ACE:

Angiotensin-converting enzyme

AT-II:

Angiotensin II

BSA:

Bovine serum albumin

CO:

Carbon monoxide

COX:

Cyclooxygenase

CT:

Computer topography

EPR:

Enhanced permeability and retention

HIF-1α:

Hypoxia-inducible factor 1 alpha

HO-1:

Heme oxygenase-1

HPMA:

Hydroxypropyl methacrylamide

ISDN:

Isosorbide dinitrate

IgG:

Immunoglobulin G

NADPH:

Nicotinamide adenine dinucleotide phosphate

NCS:

Neocarzinostatin

NG:

Nitroglycerin

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PEG:

Polyethylene glycol

SCID:

Severe combined immune deficiency

SEM:

Scanning electron microscopy

SERCA:

Sarcoplasmic/endoplasmic reticulum ATPase

SMA:

Styrene maleic acid

TGF-β:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Research Institute for Drug Delivery System and Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan

    Hideaki Nakamura & Hiroshi Maeda

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  1. Hideaki Nakamura
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  2. Hiroshi Maeda
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Correspondence to Hiroshi Maeda .

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Editors and Affiliations

  1. UCL School of Pharmacy, University College London, London, United Kingdom

    Ijeoma F. Uchegbu

  2. UCL School of Pharmacy, University College London, London, United Kingdom

    Andreas G. Schätzlein

  3. Bexleyheath, United Kingdom

    Woei Ping Cheng

  4. School of Pharmacy & Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom

    Aikaterini Lalatsa

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Nakamura, H., Maeda, H. (2013). Cancer Chemotherapy. In: Uchegbu, I., Schätzlein, A., Cheng, W., Lalatsa, A. (eds) Fundamentals of Pharmaceutical Nanoscience. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9164-4_15

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