18-GA-Suc Modified Liposome Loading Cantharidin for Augmenting Hepatic Specificity: Preparation, Characterization, Antitumor Effects, and Liver-Targeting Efficiency

Zhu, Kun; Zhou, Lili; Zou, Manshu; Ning, Shuangcheng; Liu, Shulan; Zhou, Yifei; Du, Ke; Zhang, Xiaoqing; Xia, Xinhua

doi:10.1016/j.xphs.2020.03.001

Cited by 13 publications

(9 citation statements)

References 36 publications

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“…Liposomes or solid particles nanosystems containing GA on the surface have been developed by various methods, which generate micelles with sizes between 110 and 200 nm [73][74][75][76][77][78]. Since for cancer treatment, the ideal size requirement for particles is between 70 and 200 nm, the appropriate size and good dispersion would be favorable to evade the body reticuloendothelial system and accumulate in tumor tissues by EPR (enhanced permeability and retention) effect [79]. In addition to the determination of average particle size performed by dynamic light scattering (DLS) and transmittance electronic microscopy (TEM), other techniques have also been used in order to confirm the synthesis of ligands with different types of nanosystems.…”

Section: Functionalized Nanoparticles With Glycyrrhizic Acid (Gl) or Glycyrrhetinic Acid (Ga)mentioning

confidence: 99%

“…In vitro study with HepG2 cells showed that the amount of intracellular GA in GA-LPs and GAL-GA-LPs was greater than GA solution (GA-S). Zhu et al developed a liposome of CTD, a potent drug against hepatocellular carcinoma, with a GA on the surface [79]. The pharmaco- The study with Hep3B hepatoma cell line and the human MDA-MB-231 breast cell line (used as a negative control) showed that the presence of GA into the micelles enhanced the uptake into Hep3B cells [108].…”

Section: Evaluation Of Liver Drug Targetingmentioning

confidence: 99%

“…In vitro study with HepG2 cells showed that the amount of intracellular GA in GA-LPs and GAL-GA-LPs was greater than GA solution (GA-S). Zhu et al developed a liposome of CTD, a potent drug against hepatocellular carcinoma, with a GA on the surface [79]. The pharmacokinetic and biodistribution experiments on Sprague-Dawley rats revealed that the presence of the GA in the liposome surface increased more than twice the concentration of the drug in the liver compared to the liposome without GA in the surface.…”

Section: Evaluation Of Liver Drug Targetingmentioning

confidence: 99%

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Glycyrrhizic Acid and Its Hydrolyzed Metabolite 18β-Glycyrrhetinic Acid as Specific Ligands for Targeting Nanosystems in the Treatment of Liver Cancer

et al. 2021

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Glycyrrhizic acid and its hydrolyzed metabolite 18β-glycyrrhetinic acid, obtained from the plant Glycyrrhiza glabra, have numerous pharmacological activities, such as anti-inflammatory, anti-ulcerative, antiallergic, immunomodulatory, antiviral, antitumor, hepatoprotective, and antioxidant effects, and others. In addition to the pharmacological activities, in the 1980s, an interaction and uptake of these molecules by the liver was verified, which was later confirmed by other studies through the discovery of specific receptors in the hepatocytes. The presence of these specific receptors in the liver led to vectorization and delivery of drugs, by the introduction of glycyrrhizic acid or glycyrrhetinic acid on the surface of nanosystems, for the treatment of liver diseases. This review describes experimental evidence of vectorization by conjugating glycyrrhizic acid or glycyrrhetinic acid to nanosystems and delivery of antitumor drugs for the treatment of liver cancer and also describes the techniques used to perform this conjugation. We have shown that due to the existence of specific receptors for these molecules, in addition to the targeting of nanosystems to hepatocytes, nanosystems having glycyrrhizic acid or glycyrrhetinic acid on their surface had the same therapeutic effect in a significantly lower dose compared to the free drug and unconjugated nanosystems, with consequent reduction of side effects and toxicity.

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Section: Functionalized Nanoparticles With Glycyrrhizic Acid (Gl) or Glycyrrhetinic Acid (Ga)mentioning

confidence: 99%

Section: Evaluation Of Liver Drug Targetingmentioning

confidence: 99%

“…In vitro study with HepG2 cells showed that the amount of intracellular GA in GA-LPs and GAL-GA-LPs was greater than GA solution (GA-S). Zhu et al developed a liposome of CTD, a potent drug against hepatocellular carcinoma, with a GA on the surface [79]. The pharmacokinetic and biodistribution experiments on Sprague-Dawley rats revealed that the presence of the GA in the liposome surface increased more than twice the concentration of the drug in the liver compared to the liposome without GA in the surface.…”

Section: Evaluation Of Liver Drug Targetingmentioning

confidence: 99%

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Glycyrrhizic Acid and Its Hydrolyzed Metabolite 18β-Glycyrrhetinic Acid as Specific Ligands for Targeting Nanosystems in the Treatment of Liver Cancer

et al. 2021

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“…Glycyrrhetinic acid (GA) is extracted from licorice and is modified for targeting of liver cells (Zhu et al, 2019(Zhu et al, , 2020Li et al, 2020). In doxorubicin-loaded chitosan/poly(ethylene glycol)-GA nanoparticles, GA increases the affinity for liver cancer cells (Tian et al, 2010).…”

Section: Delivery Of Glycyrrhetinic Acidmentioning

confidence: 99%

Smart Responsive Nanoformulation for Targeted Delivery of Active Compounds From Traditional Chinese Medicine

et al. 2020

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Traditional Chinese medicine (TCM) has been used to treat disorders in China for ~1,000 years. Growing evidence has shown that the active ingredients from TCM have antibacterial, antiproliferative, antioxidant, and apoptosis-inducing features. However, poor solubility and low bioavailability limit clinical application of active compounds from TCM. “Nanoformulations” (NFs) are novel and advanced drug-delivery systems. They show promise for improving the solubility and bioavailability of drugs. In particular, “smart responsive NFs” can respond to the special external and internal stimuli in targeted sites to release loaded drugs, which enables them to control the release of drug within target tissues. Recent studies have demonstrated that smart responsive NFs can achieve targeted release of active compounds from TCM at disease sites to increase their concentrations in diseased tissues and reduce the number of adverse effects. Here, we review “internal stimulus–responsive NFs” (based on pH and redox status) and “external stimulus–responsive NFs” (based on light and magnetic fields) and focus on their application for active compounds from TCM against tumors and infectious diseases, to further boost the development of TCM in modern medicine.

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“…There are many specific binding sites on the liver cancer cell membrane that can bind to GA, and the binding of GA to these sites is saturable and highly specific [ 32 , 33 ]. Folate receptor (FR) is a glycosylated phosphatidylinositol-linked transmembrane single-chain glycoprotein.…”

Section: Introductionmentioning

confidence: 99%

Development of Glycyrrhetinic Acid and Folate Modified Cantharidin Loaded Solid Lipid Nanoparticles for Targeting Hepatocellular Carcinoma

Wang

Ning

et al. 2022

Molecules

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Cantharidin (CTD) is the major component of anticancer drugs obtained from Mylabris Cichorii and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75–110 nm with size dispersion (PDI) within the range of 0.19–0.50 and zeta-potential approximately –10 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability—their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC.

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18-GA-Suc Modified Liposome Loading Cantharidin for Augmenting Hepatic Specificity: Preparation, Characterization, Antitumor Effects, and Liver-Targeting Efficiency

Cited by 13 publications

References 36 publications

Glycyrrhizic Acid and Its Hydrolyzed Metabolite 18β-Glycyrrhetinic Acid as Specific Ligands for Targeting Nanosystems in the Treatment of Liver Cancer

Glycyrrhizic Acid and Its Hydrolyzed Metabolite 18β-Glycyrrhetinic Acid as Specific Ligands for Targeting Nanosystems in the Treatment of Liver Cancer

Smart Responsive Nanoformulation for Targeted Delivery of Active Compounds From Traditional Chinese Medicine

Development of Glycyrrhetinic Acid and Folate Modified Cantharidin Loaded Solid Lipid Nanoparticles for Targeting Hepatocellular Carcinoma

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