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

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 alpha-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 alpha-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 MSNBAMLET 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 alpha-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.

Automated summary

This study developed oleic acid-modified mesoporous silica nanoparticles (OA-MSNs) conjugated with bovine alpha-lactalbumin as a potential drug delivery system for the anticancer drug docetaxel (DTX). The resulting MSN-BAMLET/DTX exhibited sustained and pH-responsive drug release behavior, enhanced cytotoxic effect against cancer cells, improved dispersion in solution, and inhibitory effect on cancer cell migration. The protein corona analysis showed low adsorption of plasma proteins on the alpha-lactalbumin coated siliceous composite, indicating its potential for long circulation. In vivo study demonstrated the effective cancer ablation and prolonged survival with MSN-BAMLET/DTX, suggesting its potential as a manipulable nanoplatform for therapeutic applications.