The enhanced permeability and retention (EPR) effect is a controversial concept by which molecules of certain sizes (typically
liposomes
A liposome is a small artificial Vesicle (biology and chemistry), vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, lipo ...
,
nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues.
The general explanation that is given for this phenomenon is that, in order for tumor cells to grow quickly, they must stimulate the production of blood vessels.
VEGF and other growth factors are involved in cancer
angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...
. Tumor cell aggregates as small as 150–200
μm
The micrometre ( international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American spelling), also commonly known as a micron, is a unit of length in the International System of Unit ...
, start to become dependent on blood supply carried out by neovasculature for their nutritional and oxygen supply. These newly formed tumor vessels are usually abnormal in form and architecture. They are poorly aligned defective
endothelial cells with wide fenestrations, lacking a
smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
layer, or innervation with a wider
lumen, and impaired functional receptors for
angiotensin II
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...
. Furthermore, tumor tissues usually lack effective
lymphatic drainage
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
. All of these factors lead to abnormal molecular and fluid transport dynamics, especially for macromolecular drugs. This phenomenon is referred to as the "enhanced permeability and retention (EPR) effect" of macromolecules and lipids in solid tumors. The EPR effect is further enhanced by many pathophysiological factors involved in enhancement of the extravasation of macromolecules in solid tumor tissues. For instance,
bradykinin,
nitric oxide
Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...
/
peroxynitrite,
prostaglandins, vascular permeability factor (also known as vascular endothelial growth factor VEGF),
tumor necrosis factor and others. One factor that leads to the increased retention is the lack of lymphatics around the tumor region which would filter out such particles under normal conditions.
The EPR effect is usually employed to describe nanoparticle and liposome delivery to cancer tissue.
One of many examples is the work regarding thermal
ablation with gold
nanoparticles
A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 1 ...
. Halas, West and coworkers have shown a possible complement to
radiation
In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes:
* ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visi ...
and
chemotherapy in cancer therapy, wherein once
nanoparticles
A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 1 ...
are at the cancer site they can be heated up in response to a skin penetrating near IR
laser (
Photothermal effect). This therapy has shown to work best in conjunction with
chemotherapeutics or other cancer therapies. Although the EPR effect has been postulated to carry the
nanoparticles
A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 1 ...
and spread inside the cancer tissue, only a small percentage (0.7% median) of the total administered nanoparticle dose is usually able to reach a solid tumor.
See also
*
Hiroshi Maeda (chemist)
References
{{DEFAULTSORT:Enhanced Permeability And Retention Effect
Oncology