Negatively charged Cu 1.33 S 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 1.33 S nanochains have shown a higher cellular uptake level in 4T1 cells than Cu 1.33 S 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 1.33 S nanochains have no obvious toxic effect. The Cu 1.33 S 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 (Δ T = 46 °C) at 5 min. These results reveal the feasibility of the Cu 1.33 S nanochains as a photothermal agent.