How do tumors sustain their growth rate?
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?
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. |
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Albumin, a natural carrier
of lipophilic
molecules,
delivers nutrients to
tumors to support
their rapid
growth
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