Targeted doxorubicin delivery to liver cancer cells by PEGylated mesoporous silica nanoparticles with a pH-dependent release profile

A layer of PEG (poly(ethylene glycol))-galactose was successfully grafted onto the external surface of mesoporous silica nanoparticles (MSNs) via a new silane-free approach, while the internal surface of MSNs was preserved for the encapsulation of the widely used anti-cancer drug of doxorubicin (DOX). The nanosized morphology and ordered structure of the synthesized drug delivery vehicles were verified by XRD and TEM observations. The successful grafting of PEG layer and peripherally exposed galactose ligands on the external surface of MSNs (abbreviated as MSNs-P/G) was confirmed by FT-IR and solid 13C NMR. The high-density PEG layer effectively reduced the human serum protein (HSP) adsorbance to the surface of MSNs. The maximum DOX loading amount reached as high as 900 mg/g and the loaded drug released in a pH-dependent way. Both confocal laser scanning microscopy (CLSM) observation and flow cytometry measurements supported the facts that cellular uptake of MSNs-P/G was significantly higher than that of the pristine MSNs benefitting from the galactose-receptor-mediated endocytosis process. This was consistent with the higher cytotoxicity observed with the DOX@MSNs-P/G against the HepG2 cell line by MTT measurements.

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► A silane-free route was developed to graft PEG onto the external surface of MSNs.
► The combined goals of drug delivery and liver cancer cell targeting were achieved.
► The loaded DOX demonstrated a pH-dependent release feature.
► DOX was more effectively delivered to targeted cells and induced their apoptosis.