Drug-loaded oleic-acid grafted mesoporous silica nanoparticles conjugated with α-lactalbumin resembling BAMLET-like anticancer agent with improved biocompatibility and therapeutic efficacy

Abstract

Despite its prominent therapeutic efficacy, chemotherapy has raised serious concerns due to the severe adverse effects and multidrug resistance evoked, which propels the search for safe and green therapeutic agents. BAMLET (bovine α-lactalbumin made lethal against tumor cell) is a well-known protein-based anticancer agent of selective tumoricidal activity. Here, we prepared oleic acid-modified mesoporous silica nanoparticles (OA-MSNs) conjugated with bovine α-lactalbumin, a lipoprotein complex resembling BAMLET formed on the surface of MSNs (MSN-BAMLET) to load the anticancer drug of docetaxel (DTX). Compared to that of OA-MSNs/DTX, the obtained MSN-BAMLET/DTX with a sustained and pH-responsive drug release behaviors exhibited good biocompatibility and enhanced cytotoxic effect against cancer cells. Moreover, the presence of lipoprotein complex in MSN-BAMLET contributed to the improved dispersion of the composite in solution and the inhibitory effect on the migration of cancer cells. Furthermore, the adsorption profiles of protein corona on the obtained nanoparticles were analyzed. It was found that the marked low amount and abundance of plasma proteins were adsorbed on the α-lactalbumin coated siliceous composite demonstrated its long circulation property. Finally, in vivo study showed that MSN-BAMLET/DTX contributed to the effective cancer ablation and the prolonged survival. Therefore, the constructed MSN-BAMLET of the mesoregular structure and peculiar tumoricidal effect provides a manipulable nanoplatform as drug nanocarrier for therapeutic applications.

Keywords

• Drug delivery
• Mesoporous silica nanoparticle
• BAMLET
• α-lactalbumin
• Protein corona