Self-assembled inorganic/organic hybrid nanoparticles with multi-functionalized surfaces for active targeting drug delivery

With the aim to develop a facile strategy to prepare multi-functional drug carriers and construct a new smart drug delivery platform, we prepared KALA/heparin-biotin/heparin/chitosan/CaCO3 (KALA/HPB/HP/CTS/CaCO3) hybrid nanoparticles with pH sensitivity, active targeting properties and cell penetrating abilities. All the functional components were introduced to the nanoparticles by self-assembly. The usage of the hybrid nanoparticles as an anti-cancer drug delivery platform was investigated. For comparison, HP/CTS, HP/CTS/CaCO3 and HPB/HP/CTS/CaCO3 hybrid nanoparticles were also prepared. The sizes and size distributions of the nanoparticles were determined by dynamic light scattering (DLS). The structure and morphology of the nanoparticles were characterized by X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analyzer (TGA). Doxorubicin hydrochloride (DOX) was loaded in the hybrid nanoparticles and the in vitro release study showed that the CaCO3 containing nanoparticles exhibited pH sensitive release behavior and could efficiently sustain the drug release. In vitro cellular cytotoxicity indicated the blank hybrid nanoparticles had good biocompatibility. DOX loaded KALA/HPB/HP/CTS/CaCO3 hybrid nanoparticles exhibited the strongest tumor cell inhibition effects compared with free DOX and other DOX loaded nanoparticles because of the enhanced cell uptake caused by the cell penetrating peptide and the biotin moiety in the nanoparticles. All those results indicated that the KALA/HPB/HP/CTS/CaCO3 hybrid nanoparticles could be promising carriers for drug delivery.