Unraveling the mysteries of serum albumin—more than just a serum protein

Abstract

Serum albumin is a multi-functional protein that is able to bind and transport numerous endogenous and exogenous compounds. The development of albumin drug carriers is gaining increasing importance in the targeted delivery of cancer therapy, particularly as a result of the market approval of the paclitaxel-loaded albumin nanoparticle, Abraxane®. Considering this, there is renewed interest in isolating and characterizing albumin-binding proteins or receptors on the plasma membrane that are responsible for albumin uptake. Initially, the cellular uptake and intracellular localization of albumin was unknown due to the large confinement of the protein within the vascular and interstitial compartment of the body. Studies have since assessed the intracellular localization of albumin in order to understand the mechanisms and pathways responsible for its uptake, distribution and catabolism in multiple tissues, and this is reviewed herein.

Acoustic Cluster Therapy (ACT) enhances the therapeutic efficacy of paclitaxel and Abraxane® for treatment of human prostate adenocarcinoma in mice

“…When endothelial cells are sensing shear stress they are stimulated to actively take up fluids and particles via endocytosis [35]. It is postulated that the transcellular transport of HSA-paclitaxel by endothelial cells via the GP-60 pathway [5,6] might also be enhanced due to these effects, resulting in a higher paclitaxel concentration in the tumor tissue.…”

“…liposomes, micelles, dendrimers and nanoparticles have been employed, either to passively make use of the EPR effect, or in combination with surface ligands that actively promote accumulation in tumor tissue through biochemically affinity to specifically expressed target groups. In addition, active transport using human serum albumin has been exploited to target tumor tissue [5,6]; e.g. Abraxane® (nab-paclitaxel, paclitaxel bound to albumin).…”

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

“…Of note, albumin is synthetized in the liver but is predominantly found in extravascular locations such as the skin, gut, muscle, and bodily fluids by diffusing across fenestrated capillaries (for review, see Refs. 55,56). Our results suggest that HSA may be more relevant than bovine or human serum to induce LC-like cells in vitro and most likely in vivo differentiations.…”

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

“…Transcytosis of albumin, the major oncotic protein of serum, involves the intracellular trafficking of caveolae carrying albumin that has been taken up via multiple receptors. 4 Invagination of caveolae leads to scission from the plasmalemma by the GTPase dynamin 2 and c-src. 5,6 The vesicles move into the endothelial cell and fuse with the basolateral membrane and release albumin into the interstitial space.…”