Doxorubicin-Loaded Glycyrrhetinic Acid Modified Recombinant Human Serum Albumin Nanoparticles for Targeting Liver Tumor Chemotherapy

Abstract

Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells, glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles for targeting liver tumor cells may result in increased therapeutic efficacy and decreased adverse effects of cancer therapy. In this study, doxorubicin (DOX) loaded and glycyrrhetinic acid modified recombinant human serum albumin nanoparticles (DOX/GA-rHSA NPs) were prepared for targeting therapy for liver cancer. GA was covalently coupled to recombinant human serum albumin nanoparticles, which could efficiently deliver DOX into liver cancer cells. The resultant GA-rHSA NPs exhibited uniform spherical shape and high stability in plasma with fixed negative charge (∼-25 mV) and a size about 170 nm. DOX was loaded into GA-rHSA NPs with a maximal encapsulation efficiency of 75.8%. Moreover, the targeted NPs (DOX/GA-rHSA NPs) showed increased cytotoxic activity in liver tumor cells compared to the nontargeted NPs (DOX/rHSA NPs, DOX loaded recombinant human serum albumin nanoparticles without GA conjugating). The targeted NPs exhibited higher cellular uptake in a GA receptor-positive liver cancer cell line than nontargeted NPs as measured by both flow cytometry and confocal laser scanning microscopy. Biodistribution experiments showed that DOX/GA-rHSA NPs exhibited a much higher level of tumor accumulation than nontargeted NPs at 1 h after injection in hepatoma-bearing Balb/c mice. Therefore, the DOX/GA-rHSA NPs could be considered as an efficient nanoplatform for targeting drug delivery system for liver cancer.

Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma

“…Extensive efforts have been devoted to evaluation of different cytotoxic agents by different methods, including Metronomic capecitabine [146], gemcitabine [147], cisplatin [148] and doxorubicin [149], for treatment of advanced HCC. But the objective response rate (ORR) to a single cytotoxic regimen was merely 0-10% with no significant survival benefit [150].…”

Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma

“…There is significant interest in the use of GA as a ligand to functionalize HCC-targeting drug carriers such as nanospheres (9,10), liposomes (11), and micelles (12) to improve the anti-HCC properties. These GA modified NPs exhibited more efficient liver-or hepatocyte-targeted capacity than non-GA-modified NPs (13,14). Most importantly, GA ligands could escape shortages of some current ligands such as insufficient specificity of asialoglycoprotein receptor (15) and immune reactions caused by monoclonal antibodies and growth factor-recognizing oligopeptides (16).…”

Glycyrrhetinic Acid Functionalized Graphene Oxide for Mitochondria Targeting and Cancer Treatment In Vivo

“…In detail, the DOX concentrations in tumor were 13.5, 8.2, and 3.7 µg g −1 in GA‐GO@DOX, GO@DOX, and DOX·HCl groups, respectively (Figure a). This result showed that the GA‐GO@DOX exhibited the highest tumor‐specific drug delivery potential among the three investigated treatments, which was attributed to the GA‐mediated HepG2 tumor‐targeting property …”