Enhanced Cellular Uptake and Cytotoxicity of Doxorubicin by Self-Assembled Lactobionate-Phytosterol-Alginate Nanoparticles

Abstract

Amphiphilic self-assembled phytosterol-alginate nanoparticles (PA NPs) were prepared by hydrophobic modification of alginate with phytosterols. Lactobionate, a tumor-cell-specific ligand, was grafted to PA NPs for targeting the liver cancer cells (HepG2 cells) that overexpress asialoglycoprotein receptor (ASGP-R). The physicochemical properties of lactobionate-phytosterol-alginate (LPA) NPs were characterized. Doxorubicin (DOX), a broad spectrum anticancer agent, was encapsulated into prepared NPs by dialysis method. The recognition of prepared LPA NPs to HepG2 cells was ascertained by cytotoxicity and lactobionate competition assays. Because of ASGP-R-mediated endocytosis process, the DOX/LPA NPs had lower IC50 value to HepG2 cells than pure DOX and DOX/PA. The cytotoxicity of DOX/LPA NPs to HepG2 cells could be competitively inhibited by free lactobionate. The cellular uptake manner of pure DOX and DOX/LPA NPs was recognized by confocal laser scanning microscopy image and the quicker intracellular uptake of drug for DOX/LPA NPs over pure DOX was confirmed. The LPA NPs had the latent force as a promising drug carrier to target drugs to cancer cells overexpressing ASGP-R and avoid killing the cells of normal tissues.