Long Blood Residence and Large Tumor Uptake of Ruthenium Sulfide Nanoclusters for Highly Efficient Cancer Photothermal Therapy

Transition metal sulfide (TMS) holds great potential in cancer photothermal therapy (PTT) because of the high absorbance in the near-infrared (NIR) region. The short blood circulation time and limited tumor accumulation of TMS-based photothermal agents, however, limit their applications. Herein, we design a novel TMS-based PTT agent, ruthenium sulfide-based nanoclusters (NCs), to overcome the current limitations. We firstly develop a simple method to prepare oleic acid coated ruthenium sulfide nanodots (OA-RuS(1.7) NDs) and assemble them into water-soluble NCs via sequentially coating with denatured bovine serum albumin (dBSA) and poly(ethylene glycol) (PEG). The obtained PEG-dBSA-RuS(1.7) NCs possess excellent photothermal conversion ability. More significantly, they exhibit enhanced blood circulation time and tumor-targeting efficiency in vivo compared with other TMS-based PTT nanoagents, which may be attributed to their appropriate hydrodynamic diameter (~70 nm) and an ideal charge (~0 mV). These characteristics help the PEG-dBSA-RuS(1.7) NCs to escape the removal by the reticuloendothelial system (RES) and kidney. All these advantages enable the PEG-dBSA-RuS(1.7) NCs to selectively concentrate in tumor sites and effectively ablate the cancer cells upon NIR irradiation.