EPR effect

In cancer treatment, passive targeting of macromolecular carriers to tumors is a commonly used approach. This passive targeting is based on the enhanced permeability and retention (EPR) effect, which leads to an accumulation of the high molecular weight carrier in the tumor tissue. The EPR effect arises from the different physiology of tumor vasculature, where the vessel walls are highly porous and lack the tight junctions that are present in healthy tissue. As a result, macromolecular carriers extravasate and accumulate preferentially in tumor tissue relative to normal tissues [63, 64]. 

Micellar nanocarriers have already been applied successfully for delivery of hydro-phobic drugs [86]. These carriers are usually the product of self-assembled block copolymers, consisting of a hydrophilic block and a hydrophobic block. Generally, an ELP with a transition temperature below body temperature is used as hydrophobic block and the hydrophilic block can be an ELP with a transition temperature above body temperature or another peptide or protein. The EPR effect also directs these types of carriers towards tumor tissue. 

Fig. 5 Polypeptide vesicles demonstrate the ability to utilize the EPR effect, (a) Chemical structure of the amphiphilic block polypeptide PSar-b-PMLG. (b) Fluorescence image using fluorescently labeled PEG. Fluorescence is not observed in the cancer site although accumulation is observed in the bladder, (c) Fluorescence image using ICG-labeled vesicles, showing evidence of vesicle accumulation due to the EPR effect. Adapted from [41] with permission. Copyright 2008 American Chemical Society...

Shielded polyplexes with improved blood circulating properties are interesting tools for systemic cancer therapy (see Sect. 4.2). Nanoparticles can take advantage of the enhanced permeability and retention (EPR effect) [89] for passive tumor targeting. The EPR effect is based on the leakiness of tumor vasculature, due to neovascularization in growing tumors, combined with an inadequate lymphatic drainage. Nanoparticles with an elongated plasma circulation time can extravasate and passively accumulate at the tumor site. 

Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41 189-207... 

Hatakeyama H, Akita H, Harashima H (2011) A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect a strategy for overcoming the PEG dilemma. Adv Drug Deliv Rev 63 152-160... 

Nanosized objects perform various functions in the biomedical field. In the human body, nanosized particulate substances behave very differently from larger particles. In 1986, Maeda et al. found that the stained albumin, having a size of several nanometers, naturally accumulates in the region of cancerous tissues, which is now well known as the enhanced permeability and retention (EPR) effect. Many studies in the field of nanoparticles are based on this finding. Another application of nanoparticles is the delivery system using various polyplexes that are composed of carrier molecules and plasmid DNA or nucleic acid drugs such as antisenses and siRNA. In addition, nanofibers are mainly used for biodegradable scaffolds in tissue... 

Maeda, H., Greish, K. and Fang, J. The EPR Effect and Polymeric Drugs A Paradigm Shift for Cancer Chemotherapy in the 21st Century. Vol. 193, pp. 103-121. 

Maeda H, Wu J, Sawa T, Matsumara Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics a review. J Control Rel 2000 65 271. 

In addition to the passive targeting of tumors due to the EPR effect, active targeting of PEGylated liposomes has also been successful. A study by Huwyler and coworkers (1996), for example, showed that coupling a monoclonal antibody to the surface of PEGylated liposomes resulted in significant transfer of the liposomes across the blood-brain barrier, which is difficult to achieve otherwise. The attached... 

Maeda H, Greish K, Fang J (2006) The EPR effect and polymeric drugs a paradigm shift for cancer chemotherapy in the 21st century. Adv Polym Sci 193 103-121... 

The strategy for nanosized (<--200 nm) polyplexes to reach the tumor site after systemic in vivo delivery called passive targeting takes advantage of the enhanced permeability and retention (EPR) effect [17]. This phenomenon implies... 

Fang, J., Sawa, T., and Maeda, H. Factors and mechanism of EPR effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. Adv. Exp. Med. Biol. 519 29-49. 2003. 

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