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 toxicity of drugs. Here, the use of calcium phosphate nanoparticles functionalized with Dox and hyaluronic acid (N-Dox) to enhance Dox antiproliferative activity is reported. The effects were accessed in A-375 melanoma cells, in which N-Dox IC50 significantly decreased over 48 hours (0.14 ± 0.07 (M) compared to free drug (0.44 ± 0.25 (M) and showed selective action against A-375 when compared with HEK-293 cells. Treatment triggered DNA damage, increased nuclear area, and elicited 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.
Keywords:
Senescence; drug delivery; cytotoxicity; A-375.
HIGHLIGHTS
• N-Dox has higher activity against A-375 cells than free doxorubicin.
• The formulation has higher selectivity indices than free doxorubicin.
• Treatment induced senescence and no colonies recovered after short-term exposure.
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