The Enhanced Permeability and Retention (EPR) effect is the property by which certain sizes of molecules (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

Vascular endothelial growth factor

Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....

 and other growth factors are involved in cancer angiogenesis

Angiogenesis

Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...

. Tumor cell aggregates of size as small as 150-200 nm, 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

Endothelium

The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...

 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

Lymphatic system

The lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...

. All these factors will lead to abnormal molecular and fluid transport dynamics, especially for macromolecular drugs. Namely, this phenomenon was coined “enhanced permeability and retention (EPR)-effect” of macromolecules and lipids in solid tumors. The EPR-effect is even more enhanced by many pathophysiological factors involved in enhancement of the extravasation of macromolecules in solid tumor tissues. For instance, bradykinin

Bradykinin

Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...

, nitric oxide

Nitric oxide

Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...

 / peroxynitrite

Peroxynitrite

Peroxynitrite is the anion with the formula ONOO−. It is an unstable structural isomer of nitrate, NO3−, which has the same formula but a different structure. Although peroxynitrous acid is highly reactive, its conjugate base peroxynitrite is stable in basic solution...

, prostaglandins, vascular permeability factor (also known as vascular endothelial growth factor VEGF), tumor necrosis factor

Tumor necrosis factor

Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction...

 and others. One factor that lends to the increased retention is the lack of lymphatics around the tumor region. This allows particles to stay in the tumor longer since they aren't filtered out of the system.

The EPR effect is important for nanoparticle and liposome delivery to cancer tissue. One of many examples is the work regarding thermal ablation

Ablation

Ablation is removal of material from the surface of an object by vaporization, chipping, or other erosive processes. This occurs in spaceflight during ascent and atmospheric reentry, glaciology, medicine, and passive fire protection.-Spaceflight:...

 with gold nanoparticles. Halas, West and coworkers have shown a possible complement to cancer therapy to radiation

Radiation

In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...

 and chemotherapy

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

, wherein once nanoparticles are at the cancer site they can be heated up in response to a skin penetrating near IR laser

Laser

A laser is a device that emits light through a process of optical amplification based on the stimulated emission of photons. The term "laser" originated as an acronym for Light Amplification by Stimulated Emission of Radiation...

. This therapy has shown to work best in conjunction with chemotherapeutics or other cancer therapies. The EPR effect helps to carry the nanoparticles and spread inside the cancer tissue.