Improved antiproliferative activity of doxorubicin-loaded calcium phosphate nanoparticles against melanoma cells

Abstract

The high incidence of melanoma has received significant attention. Despite advances in early detection and standard treatment options, new strategies that improve therapy with reduced side effects are highly desirable. Several studies have demonstrated the efficiency of doxorubicin (Dox) to treat melanoma, however, side effects limit its clinical use. Drug delivery systems, especially nanostructured ones, are a useful approach to enhance antitumor activity and reduce the toxicity of drugs. Here, we report the use of calcium phosphate nanoparticles functionalized with Dox and hyaluronic acid (N-Dox) to enhance Dox antiproliferative activity. The effects were accessed in A-375 melanoma cells, in which N-Dox significantly decreased IC50 over 48 hours (0.142 {+/-} 0.07) compared to the free drug (0.44 {+/-} 0.25). Treatment triggered DNA damage, increased nuclear area, and senescent phenotype. Furthermore, it did not form colonies after 14 days of incubation preceded by short exposure treatment. These preliminary results indicate that N-Dox hold promise for melanoma treatment, reducing the minimum effective dose and perhaps a reduction in the cost of treatment.