Negatively charged Cu_1.33S nanochains: endocytic pathway, photothermal therapy and toxic effect in vivo

Negatively charged nanomaterials have good biocompatibility and low cytotoxicity, but the efficiency of their entry into cells is relatively low. Thus, striking a balance between cell transport efficiency and cytotoxicity is a challenging problem in the field of nanomedicine. In this work, negatively charged Cu_1.33S nanochains have shown a higher cellular uptake level in 4T1 cells than Cu_1.33S nanoparticles with a similar diameter and surface charge. Inhibition experiments indicate that the cellular uptake of the nanochains depends principally on the lipid-raft protein (i.e. caveolin-1) mediated pathway, although the role of clathrin cannot be ruled out. Caveolin-1 can provide short-range attraction at the membrane interface. Furthermore, by using biochemical analysis, blood routine examination and histological evaluation on healthy Sprague Dawley rats, it is found that the Cu_1.33S nanochains have no obvious toxic effect. The Cu_1.33S nanochains have an effective photothermal therapy effect of tumor ablation in vivo under low injection dosage and laser intensity. As for the best performing group (20 μg + 1 W cm^-2), the temperature of the tumor site rapidly increases within the initial 3 min and rises to a plateau of 79 °C (ΔT = 46 °C) at 5 min. These results reveal the feasibility of the Cu_1.33S nanochains as a photothermal agent.