HA-modified mesoporous Silica/hydroxyapatite hybrid targeted nanoparticles loaded with cabazitaxel and LY294002 for enhanced treatment of triple-negative breast cancer

•Hydroxyapatite-doped mesoporous silica nanoparticles loading two drugs were prepared.•CL@M/H-HA has acid-responsive release and tumor-targeting properties.•CTX and LY294002 have a synergistic effect on MDA-MB-231 cells.•CL@M/H-HA can effectively induce apoptosis in MDA-MB-231 cells. Hyaluronic acid-modified hydroxyapatite-doped mesoporous silica nanoparticle delivery system (CL@M/H-HA) co-delivering the chemotherapeutic agent cabazitaxel (CTX) and the targeted drug PI3K inhibitor LY294002, was constructed for the combination therapy of triple-negative breast cancer (TNBC). CTX and LY294002 had a synergistic effect on MDA-MB-231 cells and the two drugs could be released proportionally and synchronously from the CL@M/H-HA nanoparticles. The hydroxyapatite doped in CL@M/H-HA enabled the drug-carrying system to have a pH-responsive release property. In vitro cellular uptake experiments demonstrated that hyaluronic acid modified on the surface of nanoparticles favored the high uptake efficiency of nanoparticles by tumor cells MDA-MB-231, and nanoparticles co-loaded with CTX and LY294002 could induce more apoptosis of MDA-MB-231 cells. The fabricated dual-loaded targeted nanoparticles could improve the TNBC therapeutic efficacy, providing a promising combination therapy for TNBC.