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| 1 | Brain tumor-targeted drug delivery strategies显示文摘Despite the application of aggressive surgery,radiotherapy and chemotherapy in clinics,brain tumors are still a difficult health challenge due to their fast development and poor prognosis.Brain tumor-targeted drug delivery systems,which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue,are a promising new approach to brain tumor treatments.Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues,potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery.In this review,we briefly describe the physiological characteristics of brain tumors,including blood–brain/brain tumor barriers,the tumor microenvironment,and tumor stem cells.We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges. | Xiaoli Wei Xishan Chen Man Ying Weiyue Lu | 2014 | Acta Pharmaceutica Sinica B2014，4，3： | 14 |
| 2 | Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties:preparation, characterization and application in a vaginal drug delivery system显示文摘Lack of mucoadhesive properties is the major drawback to poloxamer 407(F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an aminofunctionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407(F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol(AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels(NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin wasrevealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407. | Liqian Ci Zhigang Huang Yu Liub Zhepeng Liu Gang Wei Weiyue Lu | 2017 | Acta Pharmaceutica Sinica B2017，7，5： | 11 |
| 3 | Liposomes and lipid disks traverse the BBB and BBTB as intact forms as revealed by two-step F?rster resonance energy transfer imaging显示文摘The blood–brain barrier(BBB) and the blood–brain tumor barrier(BBTB) prevent drug and nano-drug delivery systems from entering the brain. However, ligand-mediated nano-drug delivery systems have significantly enhanced the therapeutic treatment of glioma. In this study we investigated the mechanism especially the integrity of liposomes and lipid disks while traversing the BBB and BBTB both in vitro and in vivo. Fluorophores(DiO, DiI and DiD) were loaded into liposomes and lipid disks to form F?rster resonance energy transfer(FRET) nano-drug delivery systems. Using brain capillary endothelial cells as a BBB model, we show that liposomes and disks are present in the cytoplasm as their intact forms and traverse the BBB with a ratio of 0.68‰ and 1.67‰, respectively. Using human umbilical vein endothelial cells as BBTB model, liposomes and disks remained intact and traversed the BBTB with a ratio of 2.31‰and 8.32‰ at 3 h. Ex vivo imaging and immunohistochemical results revealed that liposomes and disks could traverse the BBB and BBTB in vivo as intact forms. In conclusion, these observations explain in part the mechanism by which nano-drug delivery systems increase the therapeutic treatment of glioma. | Tongcheng Dai Kuan Jiang Weiyue Lu | 2018 | Acta Pharmaceutica Sinica B2018，8，2： | 8 |
| 4 | In vivo retention of poloxamer-based in situhydrogels for vaginal application in mouse and rat models显示文摘The purpose of this study is to evaluate the in vivo retention capabilities of poloxamer-based in situ hydrogels for vaginal application with nonoxinol-9 as the model drug. Two in situ hydrogel formulations, which contained 18% poloxamer 407 plus 1% poloxamer 188(GEL1, relative hydrophobic)or 6% poloxamer 188(GEL2, relative hydrophilic), were compared with respect to the rheological properties, in vitro hydrogel erosion and drug release. The vaginal retention capabilities of these hydrogel formulations were further determined in two small animal models, including drug quantitation of vaginal rinsing fluid in mice and isotope tracing with99 m Tc in rats. The two formulations exhibited similar phase transition temperatures ranging from 27 to 32 1C. Increasing the content of poloxamer 188 resulted in higher rheological moduli under body temperature, but slightly accelerated hydrogel erosion and drug release. When compared in vivo, GEL1 was eliminated significantly slower in rat vagina than GEL2,while the vaginal retention of these two hydrogel formulations behaved similarly in mice. In conclusion,increases in the hydrophilic content of formulations led to faster hydrogel erosion, drug release andintravaginal elimination. Rats appear to be a better animal model than mice to evaluate the in situ hydrogel for vaginal application. | Yu Liu Fujin Yang Linglin Feng Long Yang Lingyun Chen Gang Wei Weiyue Lu | 2017 | Acta Pharmaceutica Sinica B2017，7，4： | 5 |
| 5 | Enhanced glioma-targeting and stability of ~LGICP peptide coupled with stabilized peptide ~DA7R显示文摘Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide(GICP), was previously reported as a ligand for the VAV3 protein(a Rho-GTPase guanine nucleotide exchange factor),which is mainly expressed on glioma cells; the stabilized heptapeptide ~DA7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1), and has demonstrated good neovasculature-targeting ability. By linking ~DA7R and GICP, a multi-receptor targeting molecule was obtained. The stability of these three peptides was evaluated and their targeting efficiency on tumor-related cells and models was compared. The ability of these peptides to cross the blood–tumor barrier(BTB) was also determined. The results indicate that the coupled Y-shaped peptide ~DA7R–GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide. | Mingfei Zhang Weiyue Lu | 2018 | Acta Pharmaceutica Sinica B2018，8，1： | 5 |
| 6 | Downregulation of KCTD12 contributes to melanoma stemness by modulating CD271显示文摘Objective: Cancer metastasis remains the primary cause of cancer-related death worldwide.In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells.The purpose of this study was to identify the roles of KCTD12 in cancer metastasis.Methods: The Cancer Genome Atlas(TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma(SKCM) prognosis.The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay.The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay.KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo.Results: KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM.Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells.Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo.Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown.Conclusions: This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation.Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion. | Weiyu Shen Yumei Li Bifei Li Liping Zheng Xiaodong Xie Jingqing Le Yusheng Lu Tao Li Fan Chen Lee Jia | 2019 | Cancer Biology & Medicine2019，16，3： | 4 |
| 7 | Efficacy of inverso isomer of CendR peptide on tumor tissue penetration显示文摘The dense extracellular matrix and high interstitial fluid pressure of tumor tissues prevent the ability of anti-tumor agents to penetrate deep into the tumor parenchyma for treatment effects. C-end rule(CendR) peptides can enhance the permeability of tumor blood vessels and tumor tissues via binding to neuropilin-1(NRP-1), thus aiding in drug delivery. In this study, we selected one of the CendR peptides(sequence RGERPPR) as the parent L-peptide and substituted D-amino acids for the L-amino acids to synthesize its inverso peptide D(RGERPPR). We investigated the NRP-1 binding activity and tumorpenetrating ability of D(RGERPPR). We found that the binding affinity of D(RGERPPR) with NRP-1 and the cellular uptake was significantly higher than that of RGERPPR. Evans Blue tests revealed that D(RGERPPR) exhibited improved tumor-penetrating ability in C6, U87 and A549 tumor-bearing nude mice. Using nude mice bearing A549 xenograft tumors as a model, we found that the rate of tumor growth in the group co-administered with D(RGERPPR) and gemcitabine(Gem) was significantly lower than the gemcitabine-treated group with a tumor suppression rate(TSR%) of 55.4%. Together, our results demonstrate that D(RGERPPR) is a potential tumor-penetrating peptide. | Ruifeng Wang Qing Shen Xue Li Cao Xie Weiyue Lu Songli Wang Jing Wang Dongli Wang Min Liu | 2018 | Acta Pharmaceutica Sinica B2018，8，5： | 3 |
| 8 | p-Hydroxybenzoic acid (p-HA) modified polymeric micelles for brain-targeted docetaxel delivery显示文摘Chemotherapies for brain diseases have been hampered due to the inability of transport of drug across the blood-brain barrier (BBB). In order to overcome the barrier, p-hydroxybenzoic acid (p-HA), a small molecule of benzamide analogue, was used as a ligand for brain-targeted drug delivery. The p-HA was conjugated to PEG-DSPE to form p-HA-PEG-DSPE. Docetaxel-loaded polymeric micelles were prepared by a thin-film hydration method using methoxy-poly(ethylene glycol)-distearoylphosphatidyl- ethanolamine (mPEG 2000 -DSPE) as a carrier and the p-HA-PEG-DSPE as a brain targeted material. The prepared micelles showed spherical with a mean diameter of (18±3) nm. Encapsulation efficiency and drug loading were (83.49±1.3)%, (7.7±1.2)% for un- modified micelles and (80.65±1.6)%, (7.47±1.8)% for p-HA-modified micelles, respectively. In vitro cellular uptake experiments showed that the p-HA-modified micelles increased BCECs cellular uptake by 1.2 times compared to the unmodified micelles. Ex vivo near-infrared fluorescence imaging showed that brain uptake of the p-HA-modified micelles was 1.3-1.8 times higher than that of the unmodified micelles. In vitro cytotoxicity assay against glioblastoma cell U87 MG showed that inhibition rate of the p-HA-modified micelles increased by 1.2 times compared to that of the unmodified micelles and 1.7 times compared to that of DTX. Survival time of nude mice bearing intracranial glioblastoma showed that the lifetime of saline group, Taxotere group, mPEG-DSPE/DTX micelles group and p-HA-PEG-DSPE/DTX micelles group was 22, 27, 32 and 45.8 d, representively, which indicated that anti-glioblastoma activity of DTX could be significantly enhanced by the p-HA-modified polymeric micelles. These results demonstrated that the p-HA-modified micelles could be a promising brain-targeted drug delivery system for hydrophobic drugs against glioblastoma. | ZHANG ZhiXin WEI XiaoLi ZHANG XiaoYu LU WeiYue | 2013 | Chinese Science Bulletin2013，58，21： | 3 |
| 9 | Folic acid-conjugated liposomal vincristine for multidrug resistant cancer therapy显示文摘We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maximum cytotoxicity on KBv200 cells(multidrug resistant variant)compared with any other formulations.The semi-quantitative analysis of region of interest revealed that there was a great increase in area under curve(AUC)of a near-infrared fluorescein in solid tumors due to folic acid-mediated accumulation.Folic acid-conjugated PEGylated liposomes showed a significant tumor growth inhibiting effect in vitro and in vivo.TUNEL assay revealed that folic acid-conjugated PEGylated liposomes could induce cell apoptosis much more greatly than others.This study demonstrated that it had potential application prospective for the treatment of multidrug resistant cancer. | Chenyu Wang Linglin Feng Xiangkun Yang Fei Wang Weiyue Lu | 2013 | Asian Journal of Pharmaceutical Sciences2013，8，2： | 3 |
| 10 | Elucidating the operating behavior of PEM fuel cell with nickel foam as cathode flow field显示文摘Metal foam material,which serves as an alternative replacement of the conventional flow distributor of proton exchange membrane(PEM)fuel cell,has been attracting much attention over last few decades.In this work,three-dimensional modeling work for PEM fuel cell containing metal foam as cathode flow distributor has been carried out.The fuel cell performance and operating characteristics of metal foam flow field and conventional parallel flow channel have been compared and discussed.The cell performance has been reasonably validated based on the corresponding experimental tests conducted in this study.The superior performance of PEM fuel cell with metal foam as cathode flow field benefits a lot from the uniform gas flow.The porous metal foam material provides more pathways for the water delivery at the interface of metal foam flow field and gas diffusion layer(GDL),accelerating water removal capability of cathode.Because of the significant oxygen transfer loss in diffusion limited parallel channel,the operation of PEM fuel cell with parallel channel is found to be more sensitive to cathode humidification and oxygen supply at inlet.Due to the more uniform and effective electron transport though the porous electrode,it is possible to use thinner GDL in metal foam PEM fuel cell.It is expected that this study could give a good baseline of operating behavior of PEM fuel cell with metal foam flow distributor. | HUO Sen SHI WeiYu WANG RenFang LU BingBing WANG Yang JIAO Kui HOU ZhongJun | 2021 | Science China(Technological Sciences)2021，64，5： | 2 |
| 11 | Developmental toxicity of TCBPA on the nervous and cardiovascular systems of zebrafish (Danio rerio): A combination of transcriptomic and metabolomics显示文摘Tetrachlorobisphenol A(TCBPA),a widely used halogenated flame retardant,is frequently detected in environmental compartments and human samples.However,unknown developmental toxicity and mechanisms limit the entire understanding of its effects.In this study,zebrafish(Danio rerio)embryos were exposed to various concentrations of TCBPA while a combination of transcriptomics,behavioral and biochemical analyzes as well as metabolomics were applied to decipher its toxic effects and the potential mechanisms.We found that TCBPA could interfere with nervous and cardiovascular development through focal adhesion and extracellular matrix-receptor(ECM-receptor)interaction pathways through transcriptomic analysis.Behavioral and biochemical analysis results indicated abnormal swimming behavior of zebrafish larvae.Morphological observations revealed that TCBPA could cause the loss of head blood vessels.Metabolomic analysis showed that arginine-related metabolic pathways were one of the main pathways leading to TCBPA developmental toxicity.Our study demonstrated that by using omics,TCBPA was shown to have neurological and cardiovascular developmental toxicity and the underlying mechanisms were uncovered and major pathways identified. | Wentao Liu Yifan Pan Lu Yang Yun Xie Xuanyue Chen Jing Chang Weiyu Hao Lifei Zhu Bin Wan | 2023 | Journal of Environmental Sciences2023，，5： | 2 |
| 12 | Photocatalytic HER Performance of TiO_(2)-supported Single Atom Catalyst Based on Electronic Regulation:A DFT Study显示文摘Hydrogen is a kind of sustainable clean energy.Sunlight-driven hydrogen evolution reaction(HER)from water splitting assisted by photocatalysts is very crucial for developing clean energy technologies.Single-atom catalysts,such as atomically dispersed Pt on anatase(Pt1/TiO_(2))have exhibited excellent photocatalytic HER performance.However,the role of a single atom is still elusive.The mechanism of photocatalytic HER of TiO_(2)-supported noble metal single-atom catalysts has been studied.The supported single-atom Pt could narrow the bandgap of TiO_(2),enhance the optical absorption properties,and promote the transfer of the excited electrons.Excited electrons do not participate in the process of O-H cleavage,but can participate in the process of proton reduction and greatly reduce the hydrogen evolution energy barrier.Therefore,the hydrogen evolution energy can be used as a descriptor to evaluate the activity of TiO_(2)-supported single-atom catalysts.The activity of hydrogen evolution is found to be related to the number of d-band electrons of the single noble atom on M1/TiO_(2)(M=Pd,Pt,Rh,Ir).The increase of the number of d electrons in the single atom could reduce the hydrogen evolution energy and promote the hydrogen evolution process. | SONG Weiyu LV Xintong GAO Yang WANG Lu | 2022 | Chemical Research in Chinese Universities2022，38，4： | 2 |
| 13 | Preliminary investigations into surface molecularly imprinted nanoparticles for Helicobacter pylori eradication显示文摘This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles(SMINs) designed to adhere to Helicobacter pylori(H.pylori).Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method.A fraction of Lpp20,an outer membrane protein of H.pylori known as NQA,was chosen as template and modified with myristic acid to facilitate its localization on the surface of the nanoparticles.The interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance(SPR),change in zeta potential and fluorescence polarization(FP).The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control nanoparticles.In vitro experiments also indicate that such SMINs are able to adhere to H.pylori and may be useful for H.pylori eradication. | Jiaying Han Yinjing Sun Jiapeng Hou Yuyan Wang Yu Liu Cao Xie Weiyue Lu Jun Pan | 2015 | Acta Pharmaceutica Sinica B2015，5，6： | 2 |
| 14 | Diagnosis and control of machine induced noise and vibration in steel construction显示文摘 | Lu Weiyu Wang Weihui | 2008 | Journal of Mechanical Science and Technology2008，22，： | 1 |
| 15 | Tumor-penetrating peptide functionalization enhances the anti-glioblastoma effect of doxorubicin liposomes显示文摘 | Yiyi Yang Zhiqiang Yan Daixu Wei Jian Zhong Lu Liu Lin Zhang Fei Wang Xiaoli Wei Cao Xie Weiyue Lu Dannong He | 2013 | Nanotechnology2013，，40： | 1 |
| 16 | Biological treatment of oilfield-produced water:a field pilot study 显示文摘 | Mang Lu Zhongzhi Zhang Weiyu Yu | 2009 | International Biodeterioration & Biodegradation2009，63，： | 1 |
| 17 | Multinuclear NIR luminescent 1,4 - BDC bridged Schiff - base complexes of Nd(Ⅲ)显示文摘 | Lu Xingqiang Bi Weiyu Chai Wenli | 2009 | Polyhedron2009，28，： | 1 |
| 18 | Sampling strategy for wild soybean(Glycine soja)populations based on their genetic diversity and fine-scale spatial genetic structure显示文摘A total of 892 individuals sampled from a wild soybean population in a natural reserve near the Yellow River estuary located in Kenli of Shandong Province(China)were investigated.Seventeen SSR(simple sequence repeat)primer pairs from cultivated soybeans were used to estimate the genetic diversity of the population and its variation pattern versus changes of the sample size(sub-samples),in addition to investigating the fine-scale spatial genetic structure within the population.The results showed relatively high genetic diversity of the population with the mean value of allele number(A)being 2.88,expected heterozygosity(He)0.431,Shannon diversity index(I)0.699,and percentage of poly-morphic loci(P)100%.Sub-samples of different sizes(ten groups)were randomly drawn from the population and their genetic diversity was calculated by computer simulation.The regression model of the four diversity indexes with the change of sample sizes was computed.As a result,27-52 individuals can reach 95%of total genetic variability of the population.Spatial autocorrelation analysis revealed that the genetic patch size of this wild soybean population is about 18 m.The study provided a scientific basis for the sampling strategy of wild soybean populations. | ZHU Weiyue ZHOU Taoying ZHONG Ming LU Baorong | 2007 | Frontiers in Biology2007，2，4： | 1 |
| 19 | Cyclic RGD conjugated poly(ethylene glycol)- co -poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect显示文摘 | Changyou Zhan Bing Gu Cao Xie Jin Li Yu Liu Weiyue Lu | 2009 | Journal of Controlled Release2009，，1： | 1 |
| 20 | Cyclic RGD conjugated poly(ethylene glycol)- co -poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect显示文摘 | Changyou Zhan Bing Gu Cao Xie Jin Li Yu Liu Weiyue Lu | 2009 | Journal of Controlled Release2009，，1： | 1 |
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