Self-Assembled Glycyrrhetinic Acid-Biotin-Starch Nanoparticles For Hepatocarcinoma Targeting Anticancer Drug Delivery

Starch is widely used as biomedical field,which be ascribed to its properties,such as abundant,economical,biocompatibility and biodegradability.Starch molecule contains a large number of hydrophilic hydroxyl groups,therefore starches are modified by chemical methods to obtain special properties.This paper mainly researchs a modified starch nanoparticles(NPs)which is self-assembled amphipathic nanoparticles with core/shell structures in water.Glycyrrhetinic acid-starch-biotin(GBS)NPs were synthesized by esterification,in which biotin was a hydrophobic moiety and glycyrrhetinic acid was a hepatic targeted ligand.The structure information of GBS NPs showed that Biotin and glycyrrhetinic acid has been successfully connected with the starch by nuclear magnetic resonance(NMR).The morphologies of GBS NPs were spherical.The diameter range of GBS NPs was 89-144 nm,and the mean diameter of GBS NPs was about 122 nm.It was confirmed that the CAC value of31.8μg/mL.Doxorubicin(DOX),a hydrophobic anticancer chemotherapy drug,was packaged in prepared GBS NPs by dialysis.The most LE and LC of DOX in GBS NPs were 93.4% and 3.6%.Research in PBS of pH5.29,6.47,7.38 exhibit that the commulative release rate of DOX was much slower when the pH of PBS increased.The blank GBS NPs was proved to be atoxic by MTT method.The Cytotoxicities of free DOX,DOX/BS NPs,DOX/GBS NPs were estimated by measuring their cytotoxic effect versus HepG2 cell lines using the MTT method.The half maximal inhibitory concentrations(IC50)of free DOX,DOX/BS NPs and DOX/GBS NPs respectively were6.2μg/mL,3.9μg/mL,1.3μg/mL.DOX/GBS NPs had lower IC50 value to HepG2 cells compared with free DOX and DOX/BS NPs.That indicated that DOX/GBS NPs hadtargeted effect to glycyrrhetinic acid receptor expressing tumor cells(HepG2 cells)and had obvious cytotoxic effect.The cellular uptake and internalization of free DOX and DOX/GBS NPs was studied by confocal laser scanning microscopy(CLSM)image,revealing that pattern of DOX enter into cells is passive diffusion and DOX/GBS NPs were entered into cells through glycyrrhetinic acid receptor mediated endocytosis.The GBS NPs reduced the side effects of normal cells and had a broad application prospect as a hepatic targeted drug vector.