nab® Technology

First Application of Abraxis Protosphere®: nab® Technology

When albumin is the key protein used in the ProtoSphere® technology, the process is referred to as Abraxis’ proprietary nanoparticle albumin-bound or nab® technology. The diagram below depicts the active drug surrounded by albumin. The electron micrograph shows results from the first clinical validation of nab® technology.

Transmission Electron Micrograph

©ABI 2004

How do tumors sustain their growth rate?

Albumin

Albumin, a natural carrier of lipophilic molecules, delivers nutrients to tumors to support their rapid growth

Tumors have adapted several mechanisms to meet their increasing need for nutrients. One mechanism is angiogenesis, the formation of a dense and expanding blood supply, which gives growing tumors direct access to nutrients. These nutrients are often carried to tumors by albumin, the most ubiquitous protein in the body.

Another mechanism tumors use is the exploitation of a natural pathway, known as the gp60 pathway, by which nutrients are preferentially transported across the endothelial barrier when attached to albumin. Once across the endothelial barrier, albumin is delivered within the tumor cell to the interstitium. A third mechanism, only recently discovered, is the tumor’s ability to secrete a specialized protein called SPARC(Secreted Protein Acidic and Rich in Cysteine) into the tumor’s interstitium that acts as a highly charged receptor to specifically attract and bind albumin. The SPARC protein specifically binds albumin-bound nutrients and concentrates them within the tumor’s interstitium to prevent nutrients from diffusing outside the tumor cell.

How do nanoparticle drugs leverage tumor biology?

Secreted Protein Acidic and Rich in Cysteine

SPARC, a protein overexpressed and secreted by cancer cells, binds albumin to concentrate albumin-bound cytotoxic drugs at the tumor

Drugs are delivered to tumors by leaky junctions in the blood vessels. Drugs also bind to albumin and are transported in the blood and delivered to tumors. This is accomplished first by taking advantage of the transport system (gp60 pathway) across the endothelial cells and then concentrating within the tumor interstitium by its affinity for SPARC. Finally, the water insolubility of many active chemotherapy agents is overcome by using proteins instead of additional chemicals to dissolve the active drug. The nab® technology platform may serve as the basis for developing numerous drugs for the treatment of life-threatening diseases.

Albumin process

Albumin binds to caveolin-1 receptors and causes the formation of caveolae, to transport albumin across the endothelial membrane Transytosis is the transport of albumin across the endothelial barrier from within the blood vessel to the tumor’s interstitium SPARC is then secreted by the tumor to attract and retain albumin-bound nutrients within the tumor cell