One major challenge in cancer nanotechnology is how to selectively deliver nanoparticles to cancer cells. Targeting ligands that confer ‘smartness’ (biological recognition) to nanoparticles play a vital role in the targeted delivery of nanoparticles. During C-CCNE Phase 1, the Targeting Ligand Core at Carolina CCNE has developed different monovalent or/and multivalent ligands for the selective recognition of cancer biomarkers. We are continuing our efforts to systematically develop a series of single domain antibodies, antibody mimics and short 2’-F/2’-OMe RNA aptamers that display high affinity and selectivity for certain cancer cell surface receptors being addressed in different projects at C-CCNE, by using combinatorial library selection and directed molecular evolution technologies including mRNA-display and cell-SELEX. We focus on biomarkers on the surface of cancer cells such as EGFR that have been extensively examined and validated in lung cancer and other malignant tumors. This Core is directed by Professor Rihe Liu, who has extensive expertise in in vitro selection and directed evolution of biomolecules with desired properties from combinatorial libraries with very high diversities, particularly in the mRNA-display and SELEX technology platforms.