Baited SELEX: Drug-Directed Selection of Aptamers to PSMA for In Vivo Targeting of Prostate Cancer Xenografts in Mice

∼ 0.8 nM). Its affinity depends on both the small-molecule drug and the modified nucleosides. Appreciating the outstanding challenge of identifying agents that differentiate PSMA on tumors from salivary glands, we identify aptamers that selectively bind PSMA-expressing tumors while sparing salivary glands. Use of a PSMA-targeting pharmacophore as a molecular bait represents the first example of SELEX against specific targets expressed on tumors while avoiding binding to the same target expressed on normal tissues. The resulting aptamers represent hybrid biologics that enhance the affinity and tumor specificity of the small-molecule drug-pharmacophore.