Examples of Aptamers for Targeted Delivery

Since their original description in 1990, aptamers have been isolated to a wide variety of targets, including intracellular proteins, transmembrane proteins, soluble proteins, carbohydrates, and small molecule drugs. As of the submission of this chapter, 624 articles related to aptamers have been published, and more than 200 aptamers have been isolated (comprehensively listed in the Aptamer Database),51 and one aptamer, macugen (pegaptanib sodium), against the VEGF165 protein was recently approved by the FDA in December, 2004 for the treatment of neovascular macular degeneration,52,53 underscoring the rapid progress of aptamers from its original conception to clinical application. In choosing aptamers for targeting cancer cells, the aptamer must be directed towards receptors that are preferentially or exclusively expressed on the plasma membrane of cancer cells. Alternatively, they may be delivered to extracellular matrix molecules that are expressed preferentially in tumors. To date, several tumor-specific or tumor-associated aptamers have been isolated (reviewed by Pestourie et al.).54 A partial listing of these aptamers, as well as their size and binding characteristics, are outlined below.

Alpha-v beta-3 (avb3) integrin is a transmembrane glycoprotein that mediates numerous processes, including cell migration, cell growth, tumor growth and metastasis, angiogenesis, and vascular healing. The expression of this protein on the endothelial cells of tumor neovasculature is dramatically increased, making avb3 an interesting protein for targeting approaches.55 An 85-base-pair 2'-flouropyrimidine RNA aptamer (Apt-avb3) has been shown to bind to the avb3 protein on the surface of endothelial cells in vitro and inhibit endothelial cell proliferation and survival.56 The future in vivo use of the Apt-avb3 may require post-SELEX optimization, including size minimization to facilitate large-scale synthesis, and enhance the pharmacokinetic properties of this molecule. This aptamer may be utilized for targeted cancer diagnostic and therapeutic applications.

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