Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma

Shi, Lili; Tang, Cui; Chen, Yin

doi:10.1016/j.biomaterials.2012.06.072

Cited by 127 publications

(75 citation statements)

References 28 publications

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“…As the feed mass ratio of GA increased, theses proton peaks appearing in three kinds of copolymers were obviously increased. The phenomenon is similar to the report described by Shi et al [33]. TNBS method was used to study the substitution degrees of amino groups.…”

Section: Synthesis and Characterization Of Ga-gel Conjugatessupporting

confidence: 84%

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Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Fan

Yan

et al. 2018

Journal of Nanomaterials

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Hepatocellular carcinoma (HCC) is one of the most prevalent fatal diseases and the incidence of HCC is increasing worldwide. Polymeric micelles with targeting groups have drawn great attention as carriers for drug delivery in HCC therapy. Herein, novel glycyrrhetinic acid modified gelatin (GA-GEL) conjugates with three substitution degrees were synthesized and characterized. Doxorubicin (DOX) was applied as a model drug. DOX-loaded GA-GEL (DOX/GA-GEL) micelles were prepared by an emulsionsolvent evaporation method. The mean diameters of DOX/GA-GEL micelles were in the range of 195-235 nm. The encapsulation efficiency of DOX/GA-GEL micelles was 63.6%-96.2%, and the loading content was 8.3%-12.5%. Drug release from DOX-loaded micelles exhibited a biphasic manner in phosphate buffer solution (PBS) at pH 7.4. DOX/GA-GEL could be efficiently accumulated into human liver cancer HepG2 cells. The IC 50 values of DOX/GA-GEL-2 and DOX⋅HCl in HepG2 cells were 0.33 and 0.66 g/mL, respectively. In vivo imaging analysis demonstrated that the fluorescence signals of DiR-labeled GA-GEL-2 micelles were mainly distributed in liver and H22 orthotopic tumor, indicating that GA-GEL had the liver-targeting activity. Compared to DOX⋅HCl, DOX/GA-GEL-2 exhibited better antitumor activity in H22 orthotopic mice. Therefore, these results indicated that GA-GEL could be used as carrier of hydrophobic drug for targeting HCC.

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Section: Synthesis and Characterization Of Ga-gel Conjugatessupporting

confidence: 84%

“…Moreover, the statistical data of biodistribution showed that the fluorescence intensity of heart and kidney was negligible at 1 h (Figure 9(c)). These results infer that GA-GEL-2 micelles have remarkable targetability and possess the potential to reduce side effects of cardiotoxicity and nephrotoxicity caused by DOX [33].…”

Section: In Vivo Imaging Analysismentioning

confidence: 71%

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Fan

Yan

et al. 2018

Journal of Nanomaterials

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“…Since the discovery of the anti-viral properties of glycyrrhizin in 1979 [3], extensive studies have been done to investigate the pharmacological effects of glycyrrhizin. Recently, glycyrrhizin has been demonstrated to have both anti-inflammatory and anti-tumor effects in many types of cancer, such as glioma [4], hepatocarcinoma [5] and prostate cancer [6]. However, the effects of using glycyrrhizin in the treatment of lung cancer remain undetermined.…”

Section: Introductionmentioning

confidence: 99%

Glycyrrhizin Suppresses Lung Adenocarcinoma Cell Growth Through Inhibition of Thromboxane Synthase

Huang¹,

Chu²,

Jiang

et al. 2014

Cell Physiol Biochem

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Background/Aims: The effects of glycyrrhizin treatment in lung cancer remain undetermined, despite extensive studies of the anti-tumor activities of glycyrrhizin. Methods: Lung adenocarcinoma A549 and NCI-H23 cell lines were used in this study. Cell growth was examined by MTS assays, while apoptosis and cell cycle were determined by flow cytometric analysis. Both real-time PCR and western blotting were used to examine the expression levels of thromboxane synthase (TxAS), and TxAS activity was measured using EIA detection of the biosynthesis of TxA2. TxAS was overexpressed in NCI-H23 cells by transfection with TxAS cDNA, while TxAS was inhibited by transfection with TxAS siRNA in A549 cells. For the mouse model of lung adenocarcinoma, the effects of glycyrrhizin on tumor growth were analyzed by western blot evaluation of TxAS, PTEN and survivin. TxAS activity was determined by EIA assay. Results: Glycyrrhizin suppressed cell growth in A549 cells, but not in NCI-H23 cells, by induction of apoptosis. TxAS was overexpressed in A549 cells, but the TxAS levels in NCI-H23 cells were minimal. Moreover, TxAS expression and activity were suppressed by glycyrrhizin. Glycyrrhizin had no additive effects with TxAS siRNA knockdown in suppressing A549 cell growth, whereas it completely suppressed cell growth of NCI-H23 cells transfected with TxAS cDNA. These results were further confirmed by the in vivo study. Conclusion: Our study suggests that the anti-tumor effect of glycyrrhizin in lung adenocarcinoma is, at least in part, TxAS-dependent. Therefore, glycyrrhizin is a promising anti-cancer agent for the treatment of lung adenocarcinoma.

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“…[1] Chemotherapy, the main treatment of HCC so far, has been limited for its poor specificity and low uptake efficiency of chemotherapeutic drugs in tumour. [2] Nanoparticulate drug delivery systems are employed to alter biodistribution, target desired cells and control the release of chemotherapeutic drugs, which offers the potential in a successful HCC therapy. These nanoparticles can be properly designed to be either passive or active targeting.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterisation andin vitrocytotoxicity studies of chelerythrine-loaded magnetic Fe₃O₄@O-carboxymethylchitosan nanoparticles

Huang

Zhou

Liang

et al. 2013

Journal of Experimental Nanoscience

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In this work, a novel, active tumour-targeting system (Fe 3 O 4 @OCMCS-CHE) was designed by surface-modifying superparamagnetic iron oxide nanoparticles (Fe 3 O 4 ) with O-carboxymethylchitosan (OCMCS) to improve their biocompatibility and ability to target specific tumour cells. The chelerythrine (CHE) was used as the model of anti-tumour drug in this system. The optimised formulation was characterised and confirmed by scanning electron microscopy (SEM), transmission electron microscope (TEM), vibrating sample magnetometer (VSM), Xray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), in vitro drug release and so on. It was found that the synthesised nanoparticles were spherical in shape with an average size of 60 nm, the drug loading content and entrapment efficiency were 8.32 AE 0.25% (w/w) and 90.65 AE 0.46% (w/w), respectively, and the saturated magnetisation reached 27.06 emu/g. The in vitro drugrelease behaviour from nanoparticles displayed a biphasic drug-release pattern with initial burst release and consequently sustained release. Also, the effect of magnetic targeted nanoparticles on the proliferation of human hepatoma cell line (HepG2) in vitro was investigated. The results from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Hochest assays suggested that the Fe 3 O 4 @OCMCS-CHE nanoparticles could effectively inhibit the proliferation of HepG2 cells, which displayed time-dependent and concentration-dependent manner. All these results indicated that the multifunctional Fe 3 O 4 @OCMCS nanoparticles possess a high drug loading efficiency, have low cytotoxicity, and are promising candidates for targeted drug delivery.

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Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma

Cited by 127 publications

References 28 publications

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Glycyrrhizin Suppresses Lung Adenocarcinoma Cell Growth Through Inhibition of Thromboxane Synthase

Preparation, characterisation andin vitrocytotoxicity studies of chelerythrine-loaded magnetic Fe₃O₄@O-carboxymethylchitosan nanoparticles

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Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma

Cited by 127 publications

References 28 publications

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Glycyrrhizin Suppresses Lung Adenocarcinoma Cell Growth Through Inhibition of Thromboxane Synthase

Preparation, characterisation andin vitrocytotoxicity studies of chelerythrine-loaded magnetic Fe3O4@O-carboxymethylchitosan nanoparticles

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Product

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Preparation, characterisation andin vitrocytotoxicity studies of chelerythrine-loaded magnetic Fe₃O₄@O-carboxymethylchitosan nanoparticles