Enhanced antitumor activity of cabazitaxel targeting CD44+ receptor in breast cancer cell line via surface functionalized lipid nanocarriers

Purpose: To investigate the properties of surface-functionalized, hyaluronic acid-coated, cabazitaxelloaded solid lipid nanoparticles (HA-CZ-SLNs) for the treatment of breast cancer.Methods: HA-CZ-SLNs were prepared by a homogenization method. Nanoparticles were designed for prolonged circulation and slow release of the drug, as well as internalization of the nanocarrier into cancer cells. The nanoparticles were evaluated using dynamic light scattering, in vitro drug release, cell cytotoxicity and uptake studies.Results: Transmission electron microscopy revealed the resultant particles to be distinct, discrete, spherical cores surrounded by HA shells with a uniform diameter of ~210 nm. In vitro release of CZ followed a biphasic pattern with sustained release throughout the study period, implying efficient delivery for treatment. Increased cytotoxicity was exerted by HA-CZ-SLNs compared with the free drug. More importantly, HA on the surface of nanoparticles interacted with CD44 receptors overexpressed on cancer cells, resulting in increased internalization in MCF-7 cells. Excess free HA competed with this uptake, indicating that nanoparticle uptake was via receptor-mediated endocytosis. This mechanism is expected to result in enhanced therapeutic efficacy for the treatment of breast cancer.Conclusion: The results indicate prolonged release and enhanced cell penetration, release and cytotoxicity of the drug, thus showing the potential application of the surface-modified nanoparticles for the treatment of breast cancer.Keywords: Cabazitaxel, Breast cancer, Hyaluronic acid, Nanoparticle, Lipid carrier, Receptor-mediated endocytosis