Synthesis of amphiphilic triblock copolymers as multidentate ligands for biocompatible coating of quantum dots

One barrier to apply current tri-octylphosphine oxide (TOPO) based quantum dots (QDs) to biomedical imaging is that the TOPO on TOPO-QDs can be replaced by the proteins in living system, which may cause the degradation of QDs and/or deactivation of protein. In order to develop biocompatible optical imaging agents, a novel triblock copolymer, designed as a multidentate ligand, was synthesized to coat quantum dot nanocrystals (QDs). The copolymer consists of a polycarboxylic acid block at one end and a polythiol block at the other end with an intervening cross-linked poly(styrene-co-divinylbenzene) block bridging the ends. The multiple mercapto groups from the polythiol block act as multidentate ligands to stabilize QDs, while the polycarboxylic acid block improves the water solubility of QDs and offers reaction sites for surface modification or conjugation with bimolecules. The cross-linked poly(styrene-co-divinylbenzene) block provides a densely compacted hydrophobic shell. This shell will act as a barrier to inhibit the degradation of QDs by preventing the diffusion of ions and small molecules into the core of QDs. This new multidentate polymer coating facilitates the transfer of QDs from organic solvent into aqueous phase. The QDs directly bound to multidentate mercapto groups instead of TOPO are less likely to be affected by the mercapto or disulfide groups within proteins or other biomolecules. Therefore, this research will provide an alternative coating material instead of TOPO to produce QDs which could be more suitable for in vivo use under complex physiological conditions.