The support-on-support concept for in-situ oligonucleotide synthesis on nanoparticles

Oligonucleotide-loaded nanoparticles, which are of interest for biomedical application, up to now, could not be prepared by in-situ synthesis, due to difficulty of handling in automated synthesizers. To overcome this problem, we have introduced the "support-on-support" concept. It is based on the reversible anchoring of nanoparticles to the surface of microparticles. These composite beads easily can be used for automated synthesis, being released after completion of chain elongations. As examples, dextran-coated magnetite nanoparticles were attached to polystyrene microparticles through (1) a gelatine or (2) a silica layer. Release involved dissolution of the bonding layer by (1) proteases or (2) alkali.