Molecular Imaging
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2016
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IF 2.216
Pu Zhang,Zhide Guo,Deliang Zhang,Chang Liu,Guibing Chen,Rongqiang Zhuang,Manli Song,Hua Wu,Xianzhong Zhang
The aim of this study is to develop a copolymer-based single-photon emission computed tomography/magnetic resonance (SPECT/MR) dual-modality imaging agent that can be labeled with both technetium-99m (99mTc) and gadolinium (Gd) and target asialoglycoprotein receptor (ASGPR) via galactose. Monomers of N-p-vinylbenzyl-6-(2-(4-dimethylamino)benzaldehydehydrazono) nicotinate (VNI) for labeling of 99mTc, 5,8-bis(carboxymethyl)-3-oxo-11-(2-oxo-2-((4-vinylbenzyl)amino)ethyl)-1-(4-vinylphenzyl)-2,5,8,11-tetraazatridecan-13-oic acid (V2DTPA) for labeling of Gd, and vinylbenzyl-O-β-d-galactopyranosyl-d-gluconamide (VLA) for targeting ASGPR were synthesized, respectively. Then the copolymer P(VLA-co-VNI-co-V2DTPA) (pVLND2) was synthesized and characterized by gel permeation chromatography, dynamic light scattering, and high-performance liquid chromatography analysis. After labeling with 99mTc and Gd simultaneously, the radiochemical purity, toxicity, relaxivity (r1), and in vivo SPECT/MR imaging in mice were evaluated. Single-photon emission computed tomography/magnetic resonance imaging and biodistribution results showed that pVLND2 could target ASGPR well. The significantly improved signal to noise ratio was observed in mice liver during MR imaging. All the results suggest that this novel kind of copolymer has the potential to be further developed as a functional SPECT/MR imaging agent.
研究领域:
医学影像学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2017
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IF 3.756
Guirong Zheng,Ruirui Zhao,Aixiao Xu,Zhichun Shen,Xian Chen,Jingwei Shao
Combination with chemotherapeutic drug and gene therapy has been proven highly effective in suppressing tumor progression. Hence, an asialoglycoprotein receptor (ASGPR)-targeting nanodrug delivery system based on mesoporous silica (MSN) nanocarrier for co-delivery of sorafenib (SO) and vascular endothelial growth factor (VEGF) targeted siRNA (siVEGF) to hepatocellular carcinoma (HCC) was successfully designed and synthesized. The structure of nanoparticles was characterized by IR, particle size, zeta potential and N2 adsorption-desorption. The nanoparticles were further evaluated for drug release, cellular uptake, transfection, cell cytotoxicity and cell cycle against HepG2 and Huh7 cells. In vitro testing demonstrated that MSN-LA delivery system could not only induce S cell cycle arrest, enhance the cytotoxicity and improve the tumor target of SO and siVEGF, but also enhance the siVEGF transfection efficiency in ASGPR-overexpressing Huh7 cells. Overall, the MSN-LA delivery system can be a promising drug carrier which could further enhance the anti-cancer efficacy of SO and siVEGF via the active targeting property of LA .
研究领域:
药剂学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2015
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IF 6.723
Yinga Wu,Jia Cai,Jingfen Han,Huricha Baigude
Tissue-specific delivery of therapeutic RNAi has great potential for clinical applications. Receptor-mediated endocytosis plays a crucial role in targeted delivery of biotherapeutics including short interfering RNA (siRNA). Previously we reported a novel Curdlan-based nanoparticle for intracellular delivery of siRNA. Here we designed a nanoparticle based on ligand-functionalized Curdlan. Disaccharides were site-specifically conjugated to 6-deoxy-6-amino Curdlan, and the cell line specificity, cellular uptake, cytotoxicity, and siRNA delivery efficiency of the corresponding disaccharide-modified 6-deoxy-6-amino-Curdlan were investigated. Observation by fluorescence microscopy as well as flow cytometry showed that galactose-containing Curdlan derivatives delivered fluorescently labeled short nucleic acid to HepG2 cells expressing ASGPR receptor but not in other cells lacking surface ASGPR protein. Moreover, highly galactose-substituted Curdlan derivatives delivered siRNA specifically to ASGPR-expressing cells and induced RNAi activities, silencing endogenous GAPDH gene expression. Our data demonstrated that galactose-functionalized 6-deoxy-6-amino-Curdlan is a promising carrier for short therapeutic nucleic acids for clinical applications.
研究领域:
生物技术
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分子生物学
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药剂学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF LIPOSOME RESEARCH
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2021
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IF 3.648
Hua Nie,Bo Qiu,Qi-Xuan Yang,Ying Zhao,Xiao-Min Liu,Ying-Ting Zhang,Fu-Lin Liao,Sheng-Yuan Zhang
In this study, we describe a novel synthesis of galactosylated lipids by lipase catalysis. Lactitol (Lac), galactose (Gal), or N-acetyl galactosamine (GalNAc) was coupled with cholesterol (CHS) as target head groups by enzyme-catalyzed regioselective esterification to produce three kinds of lipids: CHS-1-Gal, CHS-6-Gal, or CHS-6-GalNAcFootnote1. The biological effects of galactosylated lipids carrying different constitutional isomers of the pendent sugar species were investigated. LP-1-Gal (liposomes containing 5.0 molar% of CHS-1-Gal) showed strong binding to tetrameric lectins of Ricinus communis agglutinin (RCA120) in vitro, while LP-6-Gal (liposomes containing 5.0 molar% of CHS-6-Gal) and LP-6-GalNAc (liposomes containing 5.0 molar% of CHS-6-GalNAc) did not. After intravenous injection, LP-6-GalNAc, LP-1-Gal and LP-6-Gal rapidly disappeared from the blood and accumulated rapidly in liver (up to 74.88 ± 4.11%, 58.67 ± 5.75%, and 47.66 ± 4.56% of injected dose/g organ within 4 h, respectively). This is significantly higher than the uptake of unmodified liposomes (Unmod-LP) (18.67 ± 6.07%). Pre-injection of asialofetuin significantly inhibits liver uptake of Gal-liposomes (P < 0.01), with the degree of inhibition appearing in the following order: LP-6-GalNAc (73.29%) > LP-1-Gal (67.06%) > LP-6-Gal (53.61%). More importantly, LP-6-GalNAc was preferentially taken up by hepatocytes and the uptake ratio by parenchymal cells (PC) and nonparenchymal cells (NPC) (PC/NPC ratio) was 11.03 higher than LP-1-Gal (7.32), LP-6-Gal (5.83) and Unmod-LP (2.39). We suggest that liposomes containing the novel galactosylated lipid CHS-6-GalNAc have potential as drug delivery carriers for hepatocyte-selective targeting.
研究领域:
药剂学
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生物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
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IF 5.875
Yan Wang,Ruihua Ding,Zan Zhang,Cheng Zhong,Jianyi Wang,Mian Wang
Curcumin can induce cancer cell apoptosis through lysosomal permeabilization pathway. However, the poor selectivity of curcumin restricts its use in the therapy of hepatocellular carcinoma . Because galactose group can recognize ASGPR overexpressed on hepatoma cells and morpholine group can target to the lysosome, they are integrated into a dual-targeted lipid material with low toxicity. The corresponding galactose-morpholine modified liposomes loaded with curcumin (Gal-Mor-LPs) were prepared and evaluated in comparison with conventional liposomes (LPs) and galactose modified liposomes (Gal-LPs). The in vitro and in vivo hepatic targeting capacity of liposomes followed a trend of LPs < Gal-LPs < Gal-Mor-LPs. The endocytosis of Gal-Mor-LPs was competitively inhibited by galactose, which confirmed the galactose modified liposomes entered hepatoma cells via ASGPR-mediated pathway. Gal-Mor-LPs displayed more excellent lysosomal targeting efficacy than LPs and Gal-LPs due to the attraction of acidic lysosome on basic morpholine group of Gal-Mor-LPs. The in vivo tumor inhibition effects of formulations also followed a trend of free curcumin < LPs < Gal-LPs < Gal-Mor-LPs, confirming that hepatic and lysosomal dual-targeting vehicle can improve the antitumor efficacy of curcumin. Moreover, the curcumin-loaded liposomes modified with galactose and morpholine moieties show good biocompatibility in vivo .
研究领域:
药剂学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CANCER BIOLOGY & THERAPY
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2016
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IF 2.921
Yu Zhang,Xiaofeng Zhang,Jinling Zhang,Bin Sun,Lulu Zheng,Jun Li,Sixiu Liu,Guodong Sui,Zhengfeng Yin
Circulating tumor cells (CTCs) have been proposed to be an active source of metastasis or recurrence of hepatocellular carcinoma (HCC). The enumeration and characterization of CTCs has important clinical significance in recurrence prediction and treatment monitoring in HCC patients. We previously developed a unique method to separate HCC CTCs based on the interaction of the asialoglycoprotein receptor (ASGPR) expressed on their membranes with its ligand. The current study applied the ligand-receptor binding assay to a CTC-chip in a microfluidic device. Efficient capture of HCC CTCs originates from the small dimensions of microfluidic channels and enhanced local topographic interactions between the microfluidic channel and extracellular extensions. With the optimized conditions, a capture yield reached > 85% for artificial CTC blood samples. Clinical utility of the system was further validated. CTCs were detected in all the examined 36 patients with HCC, with an average of 14 ± 10/2 mL. On the contrary, no CTCs were detected in healthy, benign liver disease or non-HCC cancer subjects. The current study also successfully demonstrated that the captured CTCs on our CTC-chip were readily released with ethylene diamine tetraacetic acid (EDTA); released CTCs remained alive and could be expanded to form a spheroid-like structure in a 3-dimensional cell culture assay; furthermore, sensitivity of released CTCs to chemotherapeutic agents (sorafenib or oxaliplatin) could be effectively tested utilizing this culture assay. In conclusion, the methodologies presented here offer great promise for accurate enumeration and easy release of captured CTCs, and released CTCs could be cultured for further functional studies.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Hua Nie,Xiao-Min Liu,Qi-Xuan Yang,Xiao-Dong Luo,Ying Zhao,Sheng-Yuan Zhang
In this study, we explored the effect of the hydrophile–lipophile balance (HLB) in the linker unit of Galactose (Gal)/N-acetylgalactosamine (GalNAc) ligands on their affinity toward asialoglycoprotein receptors (ASGPRs). Two Gal/GalNAc ligands with lipophilic linkers—{(5-cholesten-3b-ol)[(2-acetamido-2-deoxy-d-galactopyranose-6-o)sebacate]} (CHS-6-GalNAc) and {(5-cholesten-3b-ol)[(d-galactopyranose-6-o)sebacate]} (CHS-6-Gal)—and two with hydrophilic linkers—{(5-cholesten-yl)[(4-O-b-D-galactopyranosyl)-D-glucitol-6-yl]sebacate} (CHS-1-Gal) and {(5-cholesten-3a-ol)[(2-acetamido-2-deoxy-d-galactopyranose-6-o)3,6-dioxa-octanedioate]} (CHS-PEG 2 -6-GalNAc)—were synthesized by enzymatic catalysis. Compared with unmodified liposomes, all Gal/GalNAc ligand–modified liposomes showed higher efficiency toward the hepatocyte target as evaluated by weighted-average overall drug-targeting efficiency ( Te* ) in vivo and HepG2 cell uptake efficiency in vitro . The ligands containing linkers with high HLB values ( i.e. , CHS-PEG 2 -6-GalNAc and CHS-1-Gal) exhibited higher ASGPR affinity than those containing linkers with low HLB values ( i.e. , CHS-6-GalNAc and CHS-6-Gal). We used molecular-dynamics (MD) simulations to investigate the structure–activity relationship between the HLB value of the linker in a ligand and ASGPR affinity. MD simulation results indicated that a Gal/GalNAc ligand with a more hydrophilic linker ( i.e. , higher HLB value) unit tended to have a higher solvent-accessible surface area (SASA), leading to lower steric hindrance for effective ASGPR recognition. The results of this study will provide an improved design for Gal/GalNAc ligand–based surface-modified liposomes with high ASGPR affinity.
研究领域:
药剂学
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生物化学
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分子生物学
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DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
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2016
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IF 7.476
Xiaoting Li,Beibei Chen,Man He,Han Wang,Guangyang Xiao,Bin Yang,Bin Hu
In this work, we demonstrate a novel method based on inductively coupled plasma mass spectrometry (ICP-MS) detection with gold nanoparticles (Au NPs) and quantum dots (QDs) labeling for the simultaneous counting of two circulating tumor cell lines (MCF-7 and HepG2 cells) in human blood . MCF-7 and HepG2 cells were captured by magnetic beads coupled with anti-EpCAM and then specifically labeled by CdSe QDs-anti-ASGPR and Au NPs-anti-MUC1, respectively, which were used as signal probes for ICP-MS measurement. Under the optimal experimental conditions, the limits of detection of 50 MCF-7, 89 HepG2 cells and the linear ranges of 200-40000 MCF-7, 300-30000 HepG2 cells were obtained, and the relative standard deviations for seven replicate detections of 800 MCF-7 and HepG2 cells were 4.6% and 5.7%, respectively. This method has the advantages of high sensitivity, low sample consumption, wide linear range and can be extended to the simultaneous detection of multiple CTC lines in human peripheral blood.
研究领域:
分析化学
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癌症研究
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
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IF 5.3
Xin Yu Liu,He Ying Mao,Shuai Hong,Cheng-Hua Jin,Hu-Lin Jiang,Ming Guan Piao
Alcoholic liver injury stands as a predominant pathogenic contributor to the global burden of liver diseases, with alcohol consumption serving as a significant determinant of worldwide morbidity and mortality. Given that liver-targeted therapy for mitigating alcoholic liver injury remains to be a major clinical challenge due to the poor specificity and instability associated with single targeting modification in actively targeted nanomedicine systems, bifunctional targeting modification may serve as a more promising strategy. Here, galactose-functionalized hyaluronic acid (Gal-HA) coated cationic solid lipid nanoparticles carrying silybin (Gal-HA/SIL-SLNPs) featuring dual-targeting hyaluronic acid (HA) and galactose (Gal) moieties, enabled specific liver surface targeting of asialoglycoprotein receptor (ASGPR) and cluster of differentiation 44 (CD44) proteins to enhance silybin uptake, while simultaneously ameliorating the deficiencies of positively charged lipid nanoparticles as drug carriers and preserving their stability in the bloodstream. Based on the findings, Gal-HA/SIL-SLNPs with excellent biocompatibility demonstrated improved cellular internalization and liver distribution, while also displaying ideal curative properties in a mouse model of alcohol-induced liver injury without causing damage to other organs. This work suggests that Gal-HA/SIL-SLNPs with dual modification may represent an encouraging approach for developing more effective liver targeted nano-drug delivery systems to achieve accurate medication for alcoholic liver injury.
研究领域:
药学
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纳米技术
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肝病学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2021
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IF 7.46
Yanjie Chen,Jie Wei,Shupei Zhang,Hong Dai,Jianying Yan,Liang Lv
Biomarkers detection is of great significance in disease screening, early diagnosis and treatment responses. Herein, a plasmonic MXene induced multi-signal readout sensing platform was proposed for portable and ultrasensitive human anti-asialoglycoprotein receptor (human anti-ASGPR) detection, a biomarker for hepatitis. The plasmonic nanohybrid Ti 3 C 2 [email protected] prepared by decorating Ti 3 C 2 MXene with copper nano-clusters (Cu NCs) presented outstanding photothermal property and catalyst activity, which was developed as a signal reporter and participate in immune recognition event. The Ti 3 C 2 [email protected] induced visual color change from moderate blue to deep blue in the oxide-reduce methylene blue (MB-MBH 2 ) colorimetric system due to Cu NCs catalyzed more methylene blue (MB) produce. And the formation of Ti 3 C 2 [email protected] /MB complex presented brilliant photo-to-thermal conversion ability, under near infrared (NIR) laser radiation, enhanced photothermal effect from Ti 3 C 2 [email protected] /MB complex triggered significantly amplified temperature elevation in a temperature-responsive soft electronic devices (SED). Simultaneously, increased temperature greatly affected the conductivity variation in SED, this can be monitored by a commercially available digital multimeter (DMM) with resistance readout and transferred the laser stimulus into measurable electrical signal. Overall, such a new multi-signal readout biosensor realized sensitive target detection with high precision, low cost and simple operation.
研究领域:
生物传感
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纳米技术
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即时诊断
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医疗器械
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）