Targeted cisplatin delivery using folic acid-conjugated carbon nanotubes in triple-negative breast cancer models

A promising strategy to achieve selective anticancer activity for tumoral cells over non-tumoral cells is the functionalization of the drugs or carriers with folic acid (FA), as folate receptor is overexpressed on the surface of cancer cells and low on normal ones. This study focused on the development of single-walled carbon nanotubes functionalized with carboxyl groups, FA, and cisplatin (SWCNT-COOH + FA+CDDP) and on the biological assessment of targeted therapy in 3D breast (MCF-12A and MDA-MB-231) and HepG2 liver spheroids by establishing cytotoxicity, cell internalization, and death. The spectral analysis revealed the complexation of the SWCNT-COOH + FA with CDDP. In vitro evaluations demonstrated the improved anticancer properties of the CDDP released from the complex against MDA-MB-231 breast cancer spheroids at concentrations of 8 and 10 µM, compared to free CDDP. Lysosomal retention, as a mechanism of cell internalization, and cell death were also highlighted, demonstrating the potential of SWCNT-COOH + FA+CDDP for applications in breast cancer therapy. However, considerable dose and time-dependent toxicity was revealed on MCF-12A healthy breast and HepG2 liver spheroids. This study proved the ability of FA-conjugated SWCNT to efficiently deliver CDDP into breast cancer spheroids and brought important contributions to understanding the side effects of drugs and nanocarriers on healthy cells.