Protein Oriented Ligation on Nanoparticles Exploiting O6-Alkylguanine-DNA Transferase (SNAP) Genetically Encoded Fusion

The use of multifunctional nanoparticles (MFN) combining the emission of detectable optical and magnetic signals and a focused targeting action is attracting broad interest in cancer diagnostics. [ 1–3 ] The selectivity in targeting cancer cells is of primary importance and is usually achieved exploiting the modifi cation of MFN with biomolecules endowed with high affi nity for specifi c cell membrane receptors. [ 4–6 ] One of the greatest challenges in designing MFN functionalized with homing peptides and proteins to optimize molecular recognition resides in the possibility to fi nely control the ligand orientation on the nanoparticle surface. [ 7 , 8 ] So far, three main approaches have been followed to reach this goal: 1) native proteins having domains with high affi nity for small peptides can be captured via ligand immobilization on MFN; [ 8 ] 2) proteins containing affi nity tags recognized by small molecules or complexes commonly utilized for protein purifi cation can be genetically modifi ed in order to introduce a recognition sequence specifi c for protein immobilization; [ 9 , 10 ] and 3) sitespecifi c conjugation can occur via chemoselective ligation. [ 11 ]