Polymer Therapeutics II

Volume 193 of the series Advances in Polymer Science pp 103-121


The EPR Effect and Polymeric Drugs: A Paradigm Shift for Cancer Chemotherapy in the 21st Century

  • H. MaedaAffiliated withBioDynamics Research Laboratory, Kumamoto University Cooperative Research Center 2081-7 Tabaru, Mashiki-machiFaculty of Pharmaceutical Sciences, Sojo University Email author 
  • , K. GreishAffiliated withBioDynamics Research Laboratory, Kumamoto University Cooperative Research Center 2081-7 Tabaru, Mashiki-machiDepartment of Cardiovascular Surgery, Graduate School of Medical Sciences
  • , J. FangAffiliated withFaculty of Pharmaceutical Sciences, Sojo UniversityDepartment of Pathology, Duke University Medical Center

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Blood vessels in tumors are different to normal blood vessels because they have abnormal architectures and impaired functional regulation. We have studied these abnormalities, in particular vascular permeability in tumors, and found greatly enhanced permeability for macromolecules, which are retained in tumors for extended periods. We named this phenomenon the “enhanced permeability and retention(EPR) effect”. This effect, related to the transport of macromolecular drugs composed of liposomes, micelles, proteinaceous or polymer-conjugated macromolecules, lipid particles, and nanoparticles into the tumor, is the hallmark of solid tumor vasculature. These macromolecular species are therefore ideal for selective delivery to tumor. The EPR effect has facilitated the development of macromolecular drugs consisting of various polymer-drug conjugates (pendant type), polymeric micelles, and liposomes that exhibit far better therapeutic efficacy and far fewer side effects than the parent low-molecular-weight compounds.

Here, we discuss various aspects of the EPR effect via examples, including the use of polymeric drugs such as SMANCS [poly(styrene-co-maleic acid-half-n-butylate) (SMA)-conjugated neocarzinostatin (NCS)]. In addition, we review our new macromolecular drug candidates that generate reactive oxygen species via a novel mode of action. Because solid tumors frequently lack antioxystress enzymes, generating oxystress in tumor tissue may be another unique anticancer strategy. Most tumor cells have a weak or limited defense system against reactive oxygen species, and the oxygen radical-generating techniques that we have developed are primarily endogenous. Consequently, an approach to cancer therapy based on the EPR effect and oxyradical induction in order to produce apoptosis appears promising.

EPR effect Drug targeting Macromolecular drugs SMANCS Cancer drug delivery Plasma half-life Reactive oxygen radicals