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Ofloxacin loaded M0S2 nanoflakes for synergistic mild-temperature photothermal/antibiotic therapy with reduced drug resistance of bacteria

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Nano Research 2020年第9期13卷 2340-2350页

作者： Yue Huang Qiang Gao Xu Li Yifan Gao haijie han Qiao Jin Ke Yao Jian Ji MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China Eye Center the 2nd Affiliated HospitalSchool of MedicineZhejiang University88 JiefangRoadHangzhou 310009China

Antibiotic resistance is an increasingly serious threat to global public health, which can lead to the decrease of the effectiveness ofantibiotics. The combination therapy of antibiotic and mild temperature photothermal therapy (PTT) is adopted to address this issue inthis work. An antibiotic-loaded nanoplatform is fabricated based on two-dimensional (2D) molybdenum disulfide (M0S2) nanoflakesas effective near-infrared (NIR) photothermal agent. The M0S2 nanoflakes is modified with positively charged quaternized chitosan(QCS) to improve the dispersion stability and enhance the interaction between M0S2 nanoflakes and bacterial membrane. TheQCS modified M0S2 nanoflakes (QCS-M0S2) is expected to adhere onto the membrane of methicillin-resistant Staphylococcusaureus (MRSA) and depolarize the bacterial membrane by local hyperthermia under NIR irradiation. A first-line antibiotic, ofloxacin(OFLX), can be loaded onto QCS-M0S2 by π-π stacking and hydrophobic interaction. Due to the combined antibiotic-photothermaltherapy, superior bactericidal ability was achieved at mild temperature (45℃) and low antibiotic concentration. Such synergisticmild-temperature photothermal/antibiotic therapy can not only avoid the damage to neighboring tissue by PTT, but also reduce thedevelopment of drug resistance, providing an innovative way for the treatment of bacterial infections.

关键词： antibacterial nanoplatform combination therapy photothermal therapy molybdenum disulfide antibiotic resistance

Polymer coated nanodiamonds as gemcitabine prodrug with enzymatic sensitivity for pancreatic cancer treatment

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Progress in Natural Science:Materials International 2020年第5期30卷 711-717页

作者： Wanying Ye haijie han Huan Li Qiao Jin Yuzhou Wu Sabyasachi Chakrabortty Tanja Weil Jian Ji MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and Engineering Zhejiang University Zhejiang Provincial Key Lab of Ophthalmology Eye Center of the Second Affiliated Hospital School of Medicine Zhejiang University School of Chemistry and Chemical Engineering Huazhong University of Science and Technology Max-Planck Institute for Polymer Research Ulm University

The fabrication of Gemcitabine(GEM) prodrug was reported to be an effective method to enhance its pancreatic cancer treatment efficiency. Here, a kind of nanocarbon-based materials, nanodiamond(ND), was selected as the nanocarrier of GEM, owing to its outstanding surface properties and non-cytotoxicity. The polyelectrolytes,polyethyleneimine and polyacrylic acid, were used to self-assemble outside ND surface through electrostatic forces, followed by attachment of polyethylene glycol to address better biocompatibility. GEM was conjugated with an enzyme-sensitive peptide gly-phe-leu-gly to build up the controlled release platform. From characterization results of dynamic laser scattering, zeta potential and transmission electron microscope, the significant improvement of ND stability in physiological condition was proved. Non-cytotoxicity of this functionalized ND carriers and cytotoxicity of the prodrug against Bx PC-3 pancreatic cancer cells were indicated by methylthiazolyl tetrazolium(MTT) assay. In vivo experiments also revealed its superior anticancer effect compared with free GEM treatment. Therefore, the combination of polymer coated NDs with high surface capability and enzymeresponsive intracellular GEM release make it possible to realize higher treatment efficiency on pancreatic tumor therapy.

关键词： Nanodiamonds Self-assembly Enzyme-sensitive Gemcitabine prodrug

A novel gatifloxacin-loaded intraocular lens for prophylaxis of postoperative endophthalmitis

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Bioactive Materials 2023年第2期20卷 271-285页

作者： Mengna Li Jing-Wei Xu Jiayong Li Wei Wang Chenqi Luo haijie han Zhi-Kang Xu Ke Yao Eye Center Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009PR China Zhejiang Provincial Key Laboratory of Ophthalmology Hangzhou310009PR China MOE Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027PR China

Postoperative endophthalmitis(POE)has been the most threatening complication after cataract surgery,which perhaps can be solved by the antibiotic-loaded intraocular lens(IOL).However,most drug-loaded IOLs demonstrate insufficient drug quantity,short release time,increased implantation-related difficulties or other noticeable *** prevent POE and to address these deficiencies,a drug-loaded copolymer IOL,prepared from poly(urethane acrylate)prepolymer,isobornyl methacrylate(IBOMA),N-vinyl-2-pyrrolidone(NVP),Irgacure 819,RUVA-93,and gatifloxacin(GAT),was rapidly fabricated via photocuring and by using a 3D-printed *** composite displayed an outstanding and controllable GAT release behavior in vitro,a high light transmittance,and a moderate refractive ***,it demonstrated improved strain stress and elongation compared with the reference commercial acrylic IOL *** vivo tests demonstrated satisfying released drug concentration at the early treatment *** vitro and in vivo studies further confirmed the remarkable bacterial inhibition and prevention of POE by the proposed IOL,which also displayed good *** findings suggested that the GAT-loaded IOL could be a promising implant to prevent and cure POE,also the proposed methods could inspire more designs for various medical applications.

关键词： Photocuring Drug delivery intraocular lens 3D printing Postoperative endophthalmitis Gatifloxacin

Emerging pro-drug and nano-drug strategies for gemcitabine-based cancer therapy

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Asian Journal of Pharmaceutical Sciences 2022年第1期17卷 35-52页

作者： haijie han Su Li Yueyang Zhong Yue Huang Kai Wang Qiao Jin Jian Ji Ke Yao Eye Center the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Zhejiang Provincial Key Lab of Ophthalmology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless,the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accordingly, it is highly crucial to fabricate efficient gemcitabine delivery systems to obtain improved therapeutic efficacy of gemcitabine. A large number of gemcitabine pro-drugs were synthesized by chemical modification of gemcitabine to improve its biostability and bioavailability. Besides,gemcitabine-loaded nano-drugs were prepared to improve the delivery efficiency. In this review article, we introduced different strategies for improving the therapeutic performance of gemcitabine by the fabrication of pro-drugs and nano-drugs. We hope this review will provide new insight into the rational design of gemcitabine-based delivery strategies for enhanced cancer therapy.

关键词： Gemcitabine Pro-drug Nano-drug Cancer therapy

维普期刊数据库

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens

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生物活性材料(英文) 2023年第5期23卷 539-550页

作者： Xiaobo Zhang Jing Wang Jingwei Xu Wen Xu Yin Zhang Chenqi Luo Shuang Ni haijie han Xingchao Shentu Juan Ye Jian Ji Ke Yao Eye Center The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009PR China Zhejiang Provincial Key Lab of Ophthalmology The Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009PR China MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhou310027PR China

Posterior capsule opacification(PCO)is the most common long-term postoperative complication of cataract surgery,leading to secondary vision *** intraocular lens(IOL)structure and appropriate pharmacological intervention,which provides physical barriers and biological inhibition,respectively,can block the migration,proliferation,and epithelial-mesenchymal transition(EMT)of lens epithelial cells(LECs)for PCO ***,a novel indomethacin-eluting IOL(INDOM-IOL)with an optimized sharper edge and a sustained drug release behavior was developed for PCO ***(INDOM),an ophthalmic non-steroidal anti-inflammatory drug(NSAID)used for postoperative ocular inflammation,was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2(COX-2)and EMT markers,including alpha-smooth muscle actin(α-SMA)and cyclin D1,but also promote the autophagy activation in ***,autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in *** novel IOL,serving as a drug delivery platform,could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 *** the rabbit PCO model,the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO *** summary,indomethacin is an effective pharmacological intervention in PCO prophylaxis,and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property,which provided a promising approach for PCO prophylaxis in clinical application.

关键词： Posterior capsule opacification Indomethacin Autophagy Drug-eluting IOLs Epithelial-mesenchymal transition

Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification

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Bioactive Materials 2022年第3期7卷 343-357页

作者： Xiaobo Zhang Kairan Lai Su Li Jing Wang Jiayong Li Wei Wang Shuang Ni Bing Lu Andrzej Grzybowski Jian Ji haijie han Ke Yao Eye Center Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouPR China Zhejiang Provincial Key Laboratory of Ophthalmology HangzhouPR China Department of Ophthalmology University of Warmia and Mazury60-554 OlsztynPoland Institute for Research in Ophthalmology Gorczyczewskiego 2/361-553 PoznanPoland MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhouPR China

Cataract is the leading cause of visual impairment,and posterior capsular opacification(PCO)is the most common long-term complication of modern cataract surgery,which can cause severe visual impairment after *** proliferation,migration,and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells(LECs)stimulated by growth factors and cytokines,are the key pathological mechanisms involved in the development of *** study demonstrated that non-steroidal anti-inflammatory drug(NSAID),bromfenac,was capable of effectively inhibiting cell migration,overexpression of EMT markers,such as fibronectin(FN),matrix metalloproteinase 2(MMP2),α-smooth muscle actin(α-SMA),and transcription factor Snail,and extracellular signal-regulated kinase(ERK)/glycogen synthase kinase-3β(GSK-3β)signaling induced by transforming growth factor-β2(TGF-β2)in *** inhibitory effect of bromfenac on TGF-β2-induced EMT was also verified on a primary lens epithelial cell model using human anterior ***,based on ultrasonic spray technology,we developed a drug-eluting intraocular lens(IOL)using poly(lactic-co-glycolic acid)(PLGA)with sustained bromfenac release ability for the prevention of PCO *** the rabbit models of cataract surgery,bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent *** conclusion,bromfenac can inhibit TGF-β2-induced cell migration and the EMT of LECs via ERK/GSK-3β/Snail *** present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs.

关键词： Posterior capsular opacification Drug-eluting IOLs Bromfenac ERK pathway Transcription factor Snail

Direct Analysis of Whole Blood by a Disposable Monolithic Column Mass Spectrometry Analysis Kit

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Chinese Journal of Chemistry 2024年第10期42卷 1073-1078页

作者： Wenxin Wang Jin han Yutong Zheng haijie Wang Chengbiao Zhu Yongyi Li Yuqi Feng Zhenwei Wei Xiangyu Wang College of Chemistry and Molecular Science Wuhan UniversityWuhanHubei 430072China School of Public Health Wuhan UniversityWuhanHubei 430072China Schoolof Bioengineering and Health Wuhan Textile UniversityWuhanHubei 430200China

A monolithic column-based mass spectrometry(MS)analysis kit was prepared for whole blood analysis with *** kit is disposable and can be used for purification,storage,transportation and direct analysis of whole *** kit mainly consists of a capillary for quantitative microsampling,a cation exchange monolithic column for purification and storage,and a syringe for loading *** kit is very friendly to various users that one can easily siphon the blood in the kit followed by rapid *** established a quantitative method using the kit with a limit detection as low as 0.33 nmol/L,and achieved more than five orders of magnitude enhancement in sensitivity compared to direct nanoelectrospray ionization MS *** column can avoid analyte exposure to environment,which helps the storage of the sample for laboratory *** relative standard deviation of immediate blood analysis and storage blood analysis within 10 d was less than 10%.This method has been successfully applied to the quantitative analysis of procainamide hydrochloride in 2μL rat *** results indicate that this disposable kit does have the potential to achieve highly sensitive quantitative MS analysis in biological samples,which is expected to become a cost-effective and powerful tool for in vitro diagnostics.

关键词： Clinical Ms Whole blood analysis Porous polymers Matrix isolation Trace analysis

Transcriptomics integrated with metabolomics reveals the mechanism of CaCl_(2)-HCl electrolyzed water-induced glucosinolate biosynthesis in broccoli sprouts

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Food Science and Human Wellness 2024年第2期13卷 801-812页

作者： Cui Li Shuhui Song Yanan He haijie Liu College of Food Science and Nutritional Engineering China Agricultural UniversityBeijing 100083China Institute of Agri-food Processing and Nutrition Beijing Academy of Agriculture and Forestry SciencesBeijing 100097China

Glucosinolates are important phytochemicals in *** investigated the effect of CaCl_(2)-HCl electrolyzed water(CHEW)on glucosinolates biosynthesis in broccoli *** results showed that CHEW treatment significantly decreased reactive oxygen species(ROS)and malondialdeh yde(MDA)contents in broccoli *** the the 8^(th)day,compared to tap water treatment,the the total glucosinolate content of broccoli sprouts with CHEW treatment increased by 10.6%and calcium content was dramatically enhanced from 14.4 mg/g DW to 22.7 mg/g *** transcriptome and metabolome analyses revealed that CHEW treatment activated ROS and calcium signaling transduction pathways in broccoli sprouts and they interacted through MAPK ***,CHEW treatment not only promoted the biosynthesis of amino acids,but also enhanced the expression of structural genes in glucosinolate synthesis through transcription factors(MYBs,bHLHs,WRKYs,etc.).The results of this study provided new insights into the regulatory network of glucosinolates biosynthesis in broccoli sprouts under CHEW treatment.

关键词： Broccoli sprouts CaCl_(2)-HCl electrolyzed water Glucosinolates Transcriptomics Metabolomics

维普期刊数据库

Automatic detection and assessment of crack development in ultra-high performance concrete in the spatial and Fourier domains

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Frontiers of Structural and Civil Engineering 2024年第3期18卷 350-364页

作者： Jixing CAO Yao ZhanG haijie HE Weibing PENG Weigang ZHAO Zhiguo YAN Hehua ZHU School of Safety Engineering and Emergency Management Shijiazhuang Tiedao UniversityShijiazhuang 050043China College of Civil Engineering and Architecture Zhejiang UniversityHangzhou 310058China College of Civil and Architectural Engineering Taizhou UniversityTaizhou 318000China College of Civil Engineering and Architecture Zhejiang University of TechnologyHangzhou 310014China Department of Geotechnical Engineering Tongji UniversityShanghai 200092China

Automatic detection and assessment of surface cracks are beneficial for understanding the mechanical performance of ultra-high performance concrete(UHPC).This study detects crack evolution using a novel dynamic mode decomposition(DMD)*** this method,the sparse matrix‘determined’from images is used to reconstruct the foreground that contains cracks,and the global threshold method is adopted to extract the crack *** application of the DMD method to the three-point bending test demonstrates the efficiency in inspecting cracks with high ***,the geometric features,including the area and its projection in two major directions,are evaluated over *** relationship between the geometric properties of cracks and load-displacement curves of UHPC is *** to the irregular shape of cracks in the spatial domain,the cracks are then transformed into the Fourier domain to assess their *** indicate that crack patterns in the Fourier domain exhibit a distinct concentration around a central ***,the power spectral density of cracks exhibits an increasing trend over *** investigation into crack evolution in both the spatial and Fourier domains contributes significantly to elucidating the mechanical behavior of UHPC.

关键词： dynamic mode decomposition ultra-high performance concrete crack detection geometric features Fourier domain