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

Zhang, Jinming; Zhang, Min; Ji, Juan; Fang, Xiefan; Pan, Xin; Wang, Ying; Wu, Chuanbin; Chen, Meiwan

doi:10.1007/s11095-015-1714-2

Cited by 48 publications

(37 citation statements)

References 45 publications

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“…To design a delivery system with active targeting and efficient stimuli-responsiveness has been promising. 40 BMP-2 is a member of the TGF-β superfamily of proteins and involved in abundant biological actions. 15 However, its poor bioavailability by fast clearance, poor permeability and Ki-67 expression, expressed as the mean ± SD.…”

Section: Discussionmentioning

confidence: 99%

“…39 Many studies have shown that the target site of GA is expressed highly in hepatoma carcinoma cells than the nontumor hepatocytes, and GA can be combined with functionalized hepatoma carcinoma cell-targeting drug carrier, including PIC micelle, to enhance the anti-hepatoma carcinoma cell properties as a ligand. 40,41 In this paper, we report GA-poly(ethylene glycol) (PEG)-b-poly(L-lysine) (PLL) as a potential BMP-2 carrier. The designed GA-PEG-b-PLL was composed of GA-PEG and PLL (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

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In vitro and in vivo protein release and anti-ischemia/<br />reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(L-lysine) nanoparticles

Fang¹,

Liu²,

Jiang³

et al. 2017

IJN

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Here, we describe a bone morphogenetic protein-2 (BMP-2) nanocarrier based on glycyrrhetinic acid (GA)-poly(ethylene glycol) (PEG)-b-poly( l -lysine) (PLL). A protein nanocarrier was synthesized, characterized and evaluated as a BMP-2 delivery system. The designed nanocarrier was synthesized based on the ring-opening polymerization of amino acid N-carboxyanhydride. The final product was measured with 1 H nuclear magnetic resonance. GA-PEG-b-PLL nanocarrier could combine with BMP-2 through electrostatic interaction to form polyion complex (PIC) micelles. BMP-2 could be rapidly and efficiently encapsulated through the GA-PEG-b-PLL nanocarrier under physiological conditions, exhibiting efficient encapsulation and sustained release. In addition, the GA-PEG-b-PLL-mediated BMP-2 delivery system could target the liver against hepatic diseases as it has GA-binding receptors. The anti-hepatic ischemia/reperfusion injury (anti-HI/RI) effect of BMP-2/GA-PEG-b-PLL PIC micelles was investigated in rats using free BMP-2 and BMP-2/PEG-b-PLL PIC micelles as controls, and the results showed that BMP-2/GA-PEG-b-PLL PIC micelles indicated significantly enhanced anti-HI/RI property compared to BMP-2 and BMP-2/PEG-b-PLL. All results suggested that GA-PEG-b-PLL could be used as a potential BMP-2 nanocarrier.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo protein release and anti-ischemia/<br />reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(L-lysine) nanoparticles

Fang¹,

Liu²,

Jiang³

et al. 2017

IJN

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“…Zhang et al reported the delivery of miR-221 antisense oligonucleotide (anti-miR-221) using negatively charged liposomes with transfer-rin (Tf) as a targeting ligand in in vitro and also in HepG2 tumor-bearing xenograft mice (Zhang, Peng, et al, 2015). …”

Section: Current Treatment Modalities For Hepatocellular Carcinomamentioning

confidence: 99%

“…GA-modified liposomal formulations of oxaliplatin, calcein, docetaxel, wogonin and also pDNA were discussed for effective targeted therapy for HCC. Zhang and colleagues studied poly (L-Histidine) (PHIS) mediated polymeric system (GA-PEG-PHIS-PLGA) with GA for targeted delivery of the anti-cancer agent andrographolide (Zhang, Zhang, et al, 2015). …”

Section: Nanomedicines and Drug Delivery For Treating Hepatocellulmentioning

confidence: 99%

Recent advances in hepatocellular carcinoma therapy

Dutta

Mahato

2017

Pharmacology & Therapeutics

233

169

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Hepatocellular carcinoma (HCC), also called malignant hepatoma, is one of the deadliest cancers due to its complexities, reoccurrence after surgical resection, metastasis and heterogeneity. Incidence and mortality of HCC are increasing in Western countries and are expected to rise as a consequence of the obesity epidemic. Multiple factors trigger the initiation and progression of HCC including chronic alcohol consumption, viral hepatitis B and C infection, metabolic disorders and age. Although Sorafenib is the only FDA approved drug for the treatment of HCC, numerous treatment modalities such as transcatheter arterial chemoembolization/transarterial chemoembolization (TACE), radiotherapy, locoregional therapy and chemotherapy have been tested in the clinics. Polymeric nanoparticles, liposomes, and micelles carrying small molecules, proteins, peptides and nucleic acids have attracted great attention for the treatment of various cancers including HCC. Herein, we discuss the pathogenesis of HCC in relation to its various recent treatment methodologies using nanodelivery of monoclonal antibodies (mAbs), small molecules, miRNAs and peptides. Synopsis of recent clinical trials of mAbs and peptide drugs has been presented with a broad overview of the pathogenesis of the disease and treatment efficacy.

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“…23 MCF-7/ ADR cells were cultured at a density of 5×10 3 cells/well in six-well plates for 24 h. The cells were treated with MIT and MIT-PFP/PPP mixed micelles and irradiated with a laser as mentioned above. After incubation for 24 h at 37°C, the cells were collected by trypsinization, washed twice with ice-cold PBS and gently suspended in 100 μL binding buffer containing 20 μg/mL Annexin V-fluorescein isothiocyanate stain for 30 min, followed by staining with PI (10 μL) for 5 min.…”

Section: Assessment Of Cell Apoptosismentioning

confidence: 99%

Polymeric mixed micelles loaded mitoxantrone for overcoming multidrug resistance in breast cancer via photodynamic therapy

Li¹,

Cai²,

Zhao³

et al. 2017

IJN

Self Cite

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Mitoxantrone (MIT) is an anticancer agent with photosensitive properties that is commonly used in various cancers. Multidrug resistance (MDR) effect has been an obstacle to using MIT for cancer therapy. Photochemical internalization, on account of photodynamic therapy, has been applied to improve the therapeutic effect of cancers with MDR effect. In this study, an MIT-poly(ε-caprolactone)-pluronic F68-poly(ε-caprolactone)/poly( d , l -lactide-co-glycolide)–poly(ethylene glycol)–poly( d , l -lactide-co-glycolide) (MIT-PFP/PPP) mixed micelles system was applied to reverse the effect of MDR in MCF-7/ADR cells via photochemical reaction when exposed to near-infrared light. MIT-PFP/PPP mixed micelles showed effective interaction with near-infrared light at the wavelength of 660 nm and exerted great cytotoxicity in MCF-7/ADR cells with irradiation. Furthermore, MIT-PFP/PPP mixed micelles could improve reactive oxygen species (ROS) levels, decrease P-glycoprotein activity, and increase the cellular uptake of drugs with improved intracellular drug concentrations, which induced cell apoptosis in MCF-7/ADR cells under irradiation, despite MDR effect, as indicated by the increased level of cleaved poly ADP-ribose polymerase. These findings suggested that MIT-PFP/PPP mixed micelles may become a promising strategy to effectively reverse the MDR effect via photodynamic therapy in breast cancer.

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

Abstract: This novel GA-PPP polymeric carrier is promising for targeted treatment of HCC.

Cited by 48 publications

References 45 publications

In vitro and in vivo protein release and anti-ischemia/<br />reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(L-lysine) nanoparticles

In vitro and in vivo protein release and anti-ischemia/<br />reperfusion injury properties of bone morphogenetic protein-2-loaded glycyrrhetinic acid-poly(ethylene glycol)-b-poly(L-lysine) nanoparticles

Recent advances in hepatocellular carcinoma therapy

Polymeric mixed micelles loaded mitoxantrone for overcoming multidrug resistance in breast cancer via photodynamic therapy

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