The
enhanced permeability and retention (EPR) effect is a controversial concept by
which molecules of certain sizes (typically liposomes, 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. Tumor cell aggregates as small as 150-200 μm, 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. Muscle Building Bodybuilding Supplement
They are poorly aligned defective endothelial
cells with wide fenestrations, lacking a smooth muscle layer, or innervation
with a wider lumen, and impaired functional receptors for angiotensin II.
Furthermore, tumor tissues usually lack effective lymphatic drainage. 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/peroxynitrite,
prostaglandins, vascular permeability factor (also known as vascular endothelial
growth factor VEGF), tumor necrosis factor and others. One factor that lends 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. Halas, West, and coworkers have shown a possible
complement to radiation and chemotherapy in cancer therapy, wherein once
nanoparticles are at the cancer site they can be heated up in response to a
skin penetrating near IR laser. 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 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
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