Dual responsive hydroxyapatite capped mesoporous silica nanoparticles for controlled delivery of Palbociclib to treat osteosarcoma

Palbociclib (PB) is a selective cyclin-dependent kinase 4 and 6 inhibitor that have been approved for treatment of osteosarcoma. In this study, dual responsive mesoporous silica nanoparticles (MSNs) were designed to effectively deliver PB to osteosarcoma cancer cells. MSNs were modified with disulfide bonds and capped with hydroxyapatite (HA) to sense the changes of glutathione and pH, respectively. The size of the prepared NPs was around 250 nm as obtained from dynamic light scattering (DLS) and transmission electron microscopy (TEM). The drug loading of the NPs was 51% and 83.6% of the drug was released in an acidic pH and glutathione-rich environment, resembling a tumor are. Higher toxicity against MG-63 cells were obtained by PB loaded MSNs compared to PB alone. Moreover, confocal microscopy displayed high internalization of the NPs into osteosarcoma cells. The PB loaded MSNs also effectively induced the apoptosis in the cells (43%) and inhibited cellular proliferation in comparison to MSNs (28.47%) and control (13.08%). PB loaded HA –capped MSNs showed higher drug release in the tumor microenvironment and enhanced cytotoxicity against cancer cells. [Display omitted]