Scientific Reports
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2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Zhang Lan,Tan LiWei,Chen LiJuan,Chen XiaoXin,Long ChaoFeng,Peng JinRong,Qian ZhiYong
Self-assembled polymeric micelles have been widely applied in drug delivery systems. In this study, we found that pH value of micellar system solution was the decisive factor of physical stability. Furthermore, the weak basic solution could maintain the solution clarification for a relative long time. To investigate the stability of polymeric micelles in different pH solutions, the micellar particle size and the docetaxel content remaining in solution were detected at predetermined time points. The crystallographic assay of freeze-drying powder was characterized by an X-ray diffractometer. In vitro release results indicated that the PBS had little influence on the sustained-release effect of docetaxel-loaded polymeric micelles (DPM). Besides, the safety of micellar formulation was determined by an MTT assay on HEK293 cells, and the anti-tumor activity was tested on MCF-7 cells. The results demonstrated that DPM adjusted with PBS (DPM (PBS)) was of low toxicity and maintained the effectiveness of docetaxel. In vivo antitumor results indicated that DPM (PBS) had better antitumor efficacy than common docetaxel injection (DTX). Thus it was concluded that regulation of micellar solution PH by PBS is a safe and effective method to improve the physical stability of DPM. It might promote the application of micellar formulation in clinical applications.
研究领域:
药剂学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2014
·Vol. 11
·期 4
·3078-3086
·
IF 1.484
Ai‑Jun Li,Yue‑Hua Zheng,Guo‑Dong Liu,Wei‑Sheng Liu,Pei‑Cheng Cao,Zhen‑Fu Bu
The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood‑brain‑tumor barrier. In the present study, cyclic Arginine‑Glycine‑Aspartic acid‑D‑Tyrosine‑Lysine [c(RGDyK)], that has a high binding affinity to integrin αvβ3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid‑polyethylene glycol (DTX‑PLA‑PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine‑Glycine‑Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX‑PLA‑PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non‑targeted micelles showed limited transport ability. Furthermore, RGD‑linked micelles showed marked anti‑glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand‑mediated drug delivery may improve the efficacy of brain cancer chemotherapy.
研究领域:
药学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Kai Yang,Zhenjie Tang,Chong Zhang,Ruide Zhang,Sheng Hu,Changjiang Lv,Jun Huang,Jiaqi Mei,Weirui Zhao,Lehe Mei
Salvianic acid A (SAA) is a catechol compound known for its diverse physiochemical functions and has significant applications in the food and pharmaceutical industries. 4-Hydroxyphenylacetate-3-hydroxylase (4HPA3H) is a critical enzyme for SAA biosynthesis, and improving its activity towards p -hydroxyphenyllactate acid (4HPLA) is essential for highly efficient SAA production in stable biosynthetic pathways. To address this, the distal site and loops of the substrate pocket were modified to improve 4HPA3H catalytic activity towards 4HPLA using computer-aided molecular modification methods. As a result, we identified and mutated two critical sites in Ec HpaB, a 4HPA3H monooxygenase from Escherichia coli : T398, a substrate loop site, and M205, a distal site. The mutants M205F, T398S, and M205F/T398S enabled 2.51-, 2.07-, and 2.20-fold increases in catalytic efficiency ( k cat / K m towards 4HPLA), respectively. Molecular dynamics simulations showed that the overall decreased flexibility of the substrate pocket loop in Ec HpaB might help improve the enzyme's catalytic activity for 4HPLA. Owing to the T398 site in the substrate pocket coming from another monomer, molecular modification of Ec HpaB with multi-monomer interactions was also worthy of attention. These findings not only enhanced the biosynthetic efficiency of SAA but also provided insights into enzyme distal site modification and the engineering of multi-monomer enzymes.
研究领域:
生物化学
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酶工程
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计算生物学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Lipeng Qiu,Lu Ge,Miaomiao Long,Qian Wang,Yan Zhang,Xiaotian Shan,Jingxiao Chen,Huijie Zhang,Xiaomei Li,Guozhong Lv,Jinghua Chen
Heparan sulfate (HS) is a kind of natural polysaccharides with good biocompatibility. And as drug carriers, it has some advantages compared to heparin. However, the preparation of HS is cumbersome and difficult, which limits its application in drug delivery. Here, we use modern separation technique combined with chromatography to establish a new preparation method of HS. The molecular weight and degree of dispersion of HS were (1.03 × 10 4 ± 107) kDa and 1.106, respectively. HS also showed low anticoagulation activity in comparison with heparin. Subsequently, novel redox-sensitive heparan sulfate-cystamine-vitamin E succinate (HS-SS-VES, HSV) micelles were designed to increase tumor selectivity and improve the therapeutic effect of doxorubicin (DOX). DOX-loaded HSV micelles (DOX/HSV) with spherical morphology had average particle size of 90–120 nm and good redox-triggered release behavior. The cell viabilities of blank micelles were >90% in both human breast cancer (MCF7) cells and African green monkey SV40-transformed kidney fibroblast (COS7) cells. However, the cytotoxicity of DOX/HSV in MCF7 cells was higher than that of COS7 cells. Flow cytometry analyses and confocal laser scanning microscopy observation indicated that DOX/HSV micelles were internalized by endocytosis, and then the drug was released quickly and entered the nuclei of tumor cells. The results demonstrate that high-purity HS can be prepared and has the potential to be further used for drug delivery in antitumor applications.
研究领域:
生物材料学
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药剂学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
Jiaojiao Chen,Yarong Song,Wenqian Yang,Jianhui Guo,Saihui Zhang,Dong Wan,Yonghui Liu,Jie Pan
Chemotherapy remains the primary treatment for cancer; however, conventional chemotherapeutic drugs have several shortcomings, including poor solubility, lack of targeting, low bioavailability, and high toxicity to healthy tissues. In order to overcome these limitations, drug delivery systems (DDS) have emerged as a promising alternative. In this study, we synthesized TPGS3350-PVGLIG-SS-DOX polymeric micelles that incorporate both extracellular MMP2/9 enzyme response and intracellular reduction response at a nanoscale level. The micelles remained stable throughout the blood circulation and only aggregated at the tumor sites, thanks to the enhanced permeability and retention (EPR) effect. Moreover, the tumor tissue showed a high expression of MMP2/9 enzymes, which resulted in the cleavage of the PVGLIG peptide sequence, ultimately leading to an improved phagocytosis efficiency. Under the action of high intracellular GSH concentration, the disulfide bond was broken and DOX was released to induce tumor cell death. The TPSD&D micelles exhibited good tumor inhibitory activity in vivo and significantly reduced toxic side effects on normal tissues. Our work provides a simple method to assemble tumor-targeted prodrug micelles to improve cancer therapy, which holds potential for clinical applications in antitumor therapy.
研究领域:
药剂学
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肿瘤学
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生物材料学
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产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2019
·
IF 2.606
Jiangxiu Niu,Liye Wang,Ming Yuan,Jingxiao Zhang,Hong Chen,Yansong Zhang
Chemotherapeutics cannot effectively reach brain glioma due to the blood-brain barrier (BBB) and blood-brain tumour barrier (BBTB). To overcome these obstacles, dual-targeting DOX micelles (GF-DOX) were developed to deliver the drug across the BBB and reach the tumour site. In this study, we investigated the BBB targeting ability and the brain delivery of GF-DOX in mice. Results showed that the cellular uptake by brain microvascular endothelial cells (BMVECs) of GF-DOX was significantly higher than that by P105-DOX through caveolae- and clathrin-mediated endocytosis. An in vivo pharmacokinetic study in rats indicated that GF-DOX significantly increased the bioavailability of DOX (4.6-fold), as opposed to the control solution. The distribution of preparations in mice showed that GF-DOX could significantly increase the amount of DOX in the brain ( P < 0.05). The survival time of tumour-bearing mice of the GF-DOX group (32 days) was significantly longer than that of the free DOX group (19 days, P = 0.024), or other controls due to the dual-targeting effect of GF-DOX. In conclusion, the dual-targeting GF-DOX could improve the efficacy of anti-tumour drugs in the treatment of brain glioma in vitro and in vivo .
研究领域:
药剂学
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肿瘤学
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神经科学
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DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2015
·Vol. 133
·期 3
·
IF 1.768
Qianqian Zheng,Xiaoyan Zhou,Hui Li,Dong Ma,Wei Xue
An amphiphilic hyperbranched polyglycerol derivative (HPG-C18) was synthesized by the anionic ring-opening copolymerization with glycidol and 1,2-epoxyloctadecane as the monomers. This hyperbranched polymer formed large complex aggregates as confirmed by dynamic light scattering and transmission electron microscopy tests. Because of its amphiphilic properties, HPG-C18 was explored to load hydrophobic docetaxel, a clinical antitumor drug, and deliver it into breast cancer cell line (MCF-7) cells. To investigate the application of the aggregates in drug delivery, blood compatibility was studied by hemolysis analysis, red blood cell observation, and thromboelastography assay. These results indicate that HPG-C18 inhibited MCF-7 proliferation effectively with good blood compatibility, and this suggested a potential application in tumor therapy. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133 , 42895.
研究领域:
材料科学
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药学
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肿瘤学
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2023
·
IF 9.9
Zhizhou Liu,Yu Yang,Xiang Zhao,Tong Wang,Liang He,Xueyan Nan,Dragoslav Vidović,Pengli Bai
Mass cytometry (MC) is an emerging bioanalytical technique for high-dimensional biomarkers interrogation simultaneously on individual cells. However, the sensitivity and multiplexed analysis ability of MC was highly restricted by the current metal chelating polymer (MCP) mass tags. Herein, a new design strategy for MC mass tags by using a commercial available and low cost classical material, polystyrene nanoparticle (PS-NP) to carry metals was reported. Unlike inorganic materials , sub-micron-grade metal-loaded polystyrene can be easily detected by MC, thus it is not essential to pursue extremely small particle size in this mass tag design strategy. An altered cell staining buffer can significantly lower the nonspecific binding (NSB) of non-functionalized PS-NPs, revealing another method to lower NSB beside surface modification. The metal doped PS-NP_Abs mass tags showed high compatibility with MCP mass tags and 5-fold higher sensitivity. By using Hf doped PS-NP_Abs as mass tags, four new MC detection channels ( 177 Hf, 178 Hf, 179 Hf and 180 Hf) were developed. In general, this work provides a new strategy in designing MC mass tags and lowering NSB, opening up possibility of introducing more potential MC mass tag candidates.
研究领域:
生物分析技术
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纳米材料科学
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医学检测
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
·
IF 9.5
Jiahao Shi,Yuhe Zhang,Bin Ma,Haiyang Yong,Delu Che,Chaolan Pan,Wei He,Dezhong Zhou,Ming Li
Poly(β-amino ester)s (PAEs) have been widely developed for gene delivery, and hydrophobic modification can further enhance their gene transfection efficiency. However, systematic manipulation of amphiphilicity of PAEs through copolymerization with hydrophobic monomers is time-consuming and, to some extent, uncontrollable. Here, a modular strategy is developed to manipulate the amphiphilicity of the PAE/DNA polyplexes. A hydrophobic polymer (DD-C12–122) and a hydrophilic polymer (DD-90–122) are synthesized separately and used as a hydrophobic module and a hydrophilic module, respectively. The amphiphilicity of polyplexes could be manipulated by changing the ratio of the hydrophobic module and hydrophilic module. Using the modular strategy, the PAE/DNA polyplexes with the highest gene transfection efficiency and safety profile as well as possible mechanisms are identified. The modular strategy provides a novel way to engineer the hydrophobicity of PAEs to improve their gene transfection and can be easily generalized and potentially extended to other polymeric gene delivery systems.
研究领域:
材料科学
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生物技术
·
药学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Xiaoying Wang,Yihang Chen,Fatima Zohra Dahmani,Lifang Yin,Jianping Zhou,Jing Yao
An amphiphilic carboxymethyl chitosan-quercetin (CQ) conjugate was designed and synthesized for oral delivery of paclitaxel (PTX) to improve its oral bioavailability by increasing its water solubility and bypassing the P-gp drug efflux pumps . CQ conjugate had low critical micelle concentration (55.14 μg/mL), and could self assemble in aqueous condition to form polymeric micelles (PMs). PTX-loaded CQ PMs displayed a particle size of 185.8 ± 4.6 nm and polydispersity index (PDI) of 0.134 ± 0.056. The drug-loading content (DL) and entrapment efficiency (EE) were 33.62 ± 1.34% and 85.63 ± 1.26%, respectively. Moreover, PTX-loaded CQ PMs displayed similar sustained-release profile in simulated gastrointestinal fluids (pH 1.2/pH 6.8) and PBS (pH 7.4). In situ intestinal absorption experiment showed that PTX-loaded CQ PMs significantly improved the effective permeability of PTX as compared to verapamil ( P < 0.01). Likewise, PTX-loaded CQ PMs significantly enhanced the oral bioavailability of PTX, resulting in strong antitumor efficacy against tumor xenograft models with better safety profile as compared to Taxol ® and Taxol ® with verapamil. Overall, the results implicate that CQ PMs are promising vehicles for the oral delivery of water-insoluble anticancer drugs.
研究领域:
药剂学
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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
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yiran Qian,Xiaoxi Chang,Mingyang Sun,Yunqi Chen,Jiachen Zang,Chenyan Lv,Guanghua Zhao,Tuo Zhang
Bioactive peptides have attracted significant attention for their potential health benefits; however, their oral administration is challenged by degradation from digestive proteases and limited intestinal absorption. In this study, we demonstrated the exceptional gastrointestinal stability of ferritin nanocages, which remained largely intact after 30 min of simulated gastric digestion and were highly resistant to intestinal proteolysis. Consistent with in vitro findings, orally administered ferritin successfully reached the intestinal tract without significant degradation in mice. We engineered a fusion protein by linking a glucagon-like peptide-1 (GLP-1) motif to the C-terminus of heteropolymer ferritin, generating HLG. Through Caco-2 monolayer assays, we confirmed that HLG absorption occurs primarily via TfR1-mediated endocytosis, followed by lysosomal trafficking and subsequent release of bioactive GLP-1. Oral administration of HLG significantly reduced blood glucose levels and food intake in type 2 diabetic mice, whereas the GLP-1 analog exenatide alone showed no such effects. These findings highlight the potential of ferritin-based nanocages as an effective oral delivery platform for bioactive peptides.
研究领域:
纳米医学
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药剂学
·
分子药理学
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生物材料
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消化系统疾病
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药物递送
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代谢性疾病
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Shulin Hou,Huili He,Haishan Yang,Chunrong Chen,Qian Wang,Zhifang Wu,Sijin Li,Jun Xie
Secreted phospholipase A2s (sPLA2s) participate in physiological function by their enzyme and receptor binding activity. Muscle-type phospholipase A2 receptor (M-type PLA2R) is the sPLA2 binding protein with the highest affinity so far, and also inhibits the enzyme activity of sPLA2. There is species specificity and pH dependence for the binding of M-type PLA2R to sPLA2. Mouse sPLA2 Group IIE (mGIIE) has been verified to have a high affinity for mouse M-type PLA2R (M-type mPLA2R) at the nanomolar scale. For further exploration of the receptor binding mechanism of GIIE, in this study, we use Alphafold Multimer to generate complex models of mGIIE with the M-type mPLA2R ectodomain, wild-type CTLD5 domain of mPLA2R, and three CTLD5 mutants, respectively. mPLA2R-mGIIE models exhibit heterogeneous extended mPLA2R conformations with uncovered sPLA2-binding surface of CTLD5 domain. Complexed models of mGIIE with wild-type and mutated mCTLD5 further confirm that helix α1 of mCTLD5, especially essential residues F838 and W842, interact with the substrate pocket of mGIIE and thus inhibit its enzyme activity. Peptides from helix α1 of mCTLD5 are verified to inhibit the enzymatic activity of mGIIE. This AI-guided research would substantially accelerate our understanding of the functional study of GIIE, and provide the lead-peptide for the further inhibitor design of sPLA2.
研究领域:
生物化学
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结构生物学
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分子生物学
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酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）