A sequential dual-locked luminescent copper nanocluster probe for tumor cell imaging and killing

A sequential dual-locked luminescent copper nanoclusters (CuNCs) probe was designed and synthesized for the specific imaging and selective killing of tumor cells. This nanoprobe was prepared by first forming a Fe³⁺-coupled tannic acid (TA)-stabilized CuNCs (CuNCs-Fe^III), which is in quenching state due to the electron transfer between CuNCs and Fe³⁺, and then coating a protectable layer of hyaluronic acid (HA) on the surface of CuNCs-Fe^III to form the final dual-locked nanoprobe (CuNCs-Fe^III@HA). When the nanoprobe of CuNCs-Fe^III@HA target enter the tumor cells through CD44-HA receptor, HAase will first digest the HA layer of the nanoprobes, and then, GSH over-expressed in tumor cells will reduce Fe³⁺ to Fe²⁺, thus restoring the fluorescence emission of CuNCs and at the same time killing the tumor cells with the hydroxyl free radicals (∙OH) produced by the Fenton reaction between Fe²⁺ and H₂O₂. This sequential dual-locked luminescent nanoprobe of CuNCs-Fe^III@HA has been successfully used for the specific imaging and selective killing of tumor cells.