Targeted Anticancer Nanoparticles Seek Out Integrin Binding Sites

A recent paper described the development of a new class of targeted nanoparticles designed to specifically target cancer cells while not interacting with normal tissues.

Investigators at the University of Alberta (Edmonton, Canada) reported in the November 14, 2012, issue of the journal Nano Letters that they had developed an unbiased multiplex “beads on a bead” strategy to isolate, characterize, and validate high affinity ligands from OBOC (One-Bead–One-Compound) molecular libraries. The peptides identified here represent novel integrin-targeted agents that can be used to develop targeted nanomedicines without the risk of increased tumor invasion and metastasis.

Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands.

The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.

Senior author Dr. John Lewis, professor of oncology at the University of Alberta, said, "We are developing smart drugs that determine which are the cancer cells and which are not, then selectively kill only the cancer cells. The drugs look for a protein that is only found in cancer cells, not normal cells. This system acts like a homing beacon for tumors. If we can use "smart" drugs that home in on tumors, we can dramatically decrease side effects for patients, lower the chance of recurrence, and hopefully increase the cancer survival rate."

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