Cancer Chemotherapy

Chapter

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.

Keywords

Nitrite Angiotensin Prostaglandin Pyran Lactobacillus 

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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Research Institute for Drug Delivery System and Faculty of Pharmaceutical SciencesSojo UniversityKumamotoJapan

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