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Nano Research 2023年第7期16卷 2695-2705页

作者： Xiaomei Wu Li Wang Kai Wang Jia Ke Sufen Li Tingting Meng Hong Yuan Qirui Zhang Fuqiang Hu College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China College of Pharmaceutical Science Shenyang Pharmaceutical UniversityShenyang 110016China

Glial cell line-derived neurotrophic factor(GDNF),a disease-modifying drug for Parkinson’s disease(PD)is in Phase 2 clinical trials(EudraCT number:2011-003866-34),however it is administered by direct intrastriatal delivery via stereotaxy,which is accompanied with intracranial infection,brain tissue damage,and other complications.In addition,because of complex administration routes,clinical trials of GDNF have yielded contrary results,largely due to differences in dose and concentration brought by intracranial device.Herein,a small molecular agonist SC79 was screened to open blood-brain barrier(BBB)and promote GDNF liposomes to get into brain.SC79 reversibly reduces the expression of claudin-5,one of dominant tight junctions of BBB.Animal study showed SC79 promoted liposomes to enter into brain parenchyma 2.43 times more than that of the control.Motor deficits of PD mice receiving SC79 and brain-targeted GDNF liposomes were recovered by 36.70%and tyrosine hydroxylase positive neurons in striatum were restored by 39.90%.Our combination therapy effectively avoids the side effects such as secondary infection and uneven delivery caused by intracranial injection,improving patients’compliance and providing valuable research ideas for the clinic.

关键词： blood-brain barrier brain delivery facilitation tight junction glial cell line-derived neurotrophic factor disease-modifying Parkinson’s disease

Cell membrane coated-nanoparticles for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3233-3254页

作者： Yingping Zeng Sufen Li Shufen Zhang Li Wang Hong Yuan Fuqiang Hu College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China

Cancer immunotherapy can effectively inhibit cancer progression by activating the autoimmune system, with low toxicity and high effectiveness. Some of cancer immunotherapy had positive effects on clinical cancer treatment. However, cancer immunotherapy is still restricted by cancer heterogeneity, immune cell disability, tumor immunosuppressive microenvironment and systemic immune toxicity. Cell membrane-coated nanoparticles(CMCNs) inherit abundant source cell-relevant functions, including “self” markers, cross-talking with the immune system, biological targeting, and homing to specific regions. These enable them to possess preferred characteristics, including better biological compatibility, weak immunogenicity, immune escaping, a prolonged circulation, and tumor targeting.Therefore, they are applied to precisely deliver drugs and promote the effect of cancer immunotherapy.In the review, we summarize the latest researches of biomimetic CMCNs for cancer immunotherapy,outline the existing specific cancer immune therapies, explore the unique functions and molecular mechanisms of various cell membrane-coated nanoparticles, and analyze the challenges which CMCNs face in clinical translation.

关键词： Biomimetic Cell membrane-coated nanoparticles Drug delivery “Self”markers Tumor targeting Cancer immunotherapy Cancer vaccines Immune checkpoint blockade inhibitors

Effect of different forms of selenium in osteoporosis rat model induced by retinoic acid

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Food Quality and Safety 2023年第2期7卷 360-369页

作者：黎海涛郭燕陈晓燕满正印张小涛 Department of Food science Zhejiang Pharmaceutical CollegeNingboChina

Osteoporosis is a typical physiological disease,the main symptoms of which are brittle fracture,bone pain and easily deformed.As an individual ages,the prevalence of osteoporosis increases year by year.In the present study,selenium with antioxidant,immunomodulatory and anti-tumor effects was used to prevent osteoporosis induced by retinoic acid.The serum calcium contents in the selenium-treated groups(sodium selenite and selenomethionine)were significantly higher(P0.05)in the activity of GOT and GPT.The content of ALP decreased obviously and the TRACP enzyme activity increased.Overall,these results showed that different forms of selenium compounds have great potential in preventing and treating osteoporosis.

关键词： Retinoic acid-induced osteoporosis rat model sodium selenite selenomethionine prevention treatment

Bavachin induces apoptosis in colorectal cancer cells through Gadd45a via the MAPK signaling pathway

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Chinese Journal of Natural Medicines 2023年第1期21卷 36-46页

作者： WANG Mengru TIAN Baopeng SHEN Jie XU Shilin LIU Cong GUAN Ling GUO Min DOU Jie college of Life science and Technology China Pharmaceutical UniversityNanjing 211198China

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia,and exhibits anti-bacterial,anti-inflammatory,anti-tumor and lipid-lowering activities.Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines.However,the anti-cancer effects and related mechanisms in colorectal cancer remain unknown.Here,we investigated the effects of bavachin on colorectal cancer in vivo and in vitro.The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis.These changes were mediated by activating the MAPK signaling pathway,which significantly up-regulated the expression of Gadd45a.Furthermore,Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis.Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin.The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer.In conclusion,these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.

关键词： Bavachin Apoptosis Colorectal cancer Gadd45a MAPK

Erratum to: Inhibition of chemotherapy-related breast tumor EMT by application of redox-sensitive siRNA delivery system CSO-ss-SA/siRNA along with doxorubicin treatment

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2022年第2期23卷 171-172页

作者： Xuan LIU Xueqing ZHOU Xuwei SHANG Li WANG Yi LI Hong YUAN Fuqiang HU College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China

The original version of this article(Liu et al.,2020)unfortunately contained some mistakes.1.Figs.7c and 7d in p.229 were incorrect.The upper left and bottom left pictures in Fig.7c were accidentally duplicated with t... 详细信息

关键词： treatment picture

A preparation strategy for protein-oriented immobilized silica magnetic beads with Spy chemistry for ligand fishing

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Journal of pharmaceutical Analysis 2022年第3期12卷 415-423页

作者： Yu Yi Jianming Hu Shenwei Ding Jianfeng Mei Xudong Wang Yanlu Zhang Jianshu Chen Guoqing Ying Institute of Biopharmaceuticals College of Pharmaceutical ScienceZhejiang University of TechnologyHangzhou310014China

Due to the complexity of bioactive ingredients in biological samples,the screening of target proteins is a complex process.Herein,a feasible strategy for directing protein immobilization on silica magnetic beads for ligand fishing based on SpyTag/SpyCatcher(ST/SC)-mediated anchoring is presented.Carboxyl functional groups on the surface of silica-coated magnetic beads(SMBs)were coupled with SC using the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide method,named SC-SMBs.The green fluorescent protein(GFP),as the capturing protein model,was ST-labeled and anchored at a specific orientation onto the surface of SC-SMBs directly from relevant cell lysates via ST/SC self-ligation.The characteristics of the SC-SMBs were studied via electron microscopy,energy dispersive spectroscopy,and Fourier transform infrared spectroscopy.The spontaneity and site-specificity of this unique reaction were confirmed via electrophoresis and fluorescence analyses.Although the alkaline stability of ST-GFP-ligated SC-SMBs was not ideal,the formed isopeptide bond was unbreakable under acidic conditions(0.05 M glycine-HCl buffer,pH 1e6)for 2 h,under 20%ethanol solution within 7 days,and at most temperatures.We,therefore,present a simple and universal strategy for the preparation of diverse protein-functionalized SMBs for ligand fishing,prompting its usage on drug screening and target finding.

关键词： EDC/Sulfo-NHS SpyTag/SpyCatcher Green fluorescent protein Silica magnetic beads Oriented immobilization Drug screening

Total synthesis and stereochemistry establishmentof tumescenamide A

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Organic Chemistry Frontiers 2022年第6期9卷 1675-1679页

作者： Hong Xue Shiming Fan Jingzhe Xu Shouxin Liu college of science Yanbian UniversityYanji133002China college of Chemical&pharmaceutical Engineering Hebei University of Science&TechnologyShijiazhuang050018China

Tumescenamide A (1), isolated from Streptomyces tumescens YM23-20, consists of a cyclic depsipeptideand a side-chain 2,4-dimethylheptanoate (Dmh). Herein, we report the first total synthesis of tumescenamide A (1) and establish its stereochemistry. The configuration of Dmh is 2S,4S and, notably, the configuration of Val is revised as D. In addition, a mild and practical method for the β-elimination of derivatives ofserine and threonine by using nano-K_(2)CO_(3) as a base was established. A highly stereoselective synthesis ofthe Dmh substructure was also developed.

关键词： synthesis stereochemistry elimination

Fluorescent intracellular imaging of reactive oxygen species and pH levels moderated by a hydrogenase mimic in living cells

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Journal of pharmaceutical Analysis 2022年第5期12卷 801-807页

作者： Xin-Yuan Hu Jia-Jing Li Zi-Wei Yang Jun Zhang Huai-Song Wang Department of pharmaceutical Analysis China Pharmaceutical UniversityNanjing210009China college of Food science and Bioengineering Tianjin Agricultural UniversityTianjin300392China

The catalytic generation of H_(2) in living cells provides a method for antioxidant therapy.In this study,an[FeFe]-hydrogenase mimic[Ru+Fe_(2)S_(2)@F127(80)]was synthesized by self-assembling polymeric pluronic F-127,catalytic[Fe_(2)S_(2)]sites,and photosensitizer Ru(bpy)_(3)^(2+).Under blue light irradiation,hydrated protons were photochemically reduced to H2,which increased the local pH in living cells(HeLa cells).The generated H2 was subsequently used as an antioxidant to decrease reactive oxygen species(ROS)levels in living cells(HEK 293T,HepG2,MCF-7,and HeLa cells).Our findings revealed that the proliferation of HEK 293T cells increased by a factor of about six times,relative to that of other cells(HepG2,MCF-7,and HeLa cells).Intracellular ROS and pH levels were then monitored using fluorescent cell imaging.Our study showed that cell imaging can be used to evaluate the ability of Ru t Fe2S2@F127 to eliminate oxidative stress and prevent ROS-related diseases.

关键词： Cell imaging [FeFe]-hydrogenase Reactive oxygen species Photocatalytic system

Heat treatment bimetallic PdAu nanocatalyst for oxygen reduction reaction

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Journal of Energy Chemistry 2020年第1期29卷 217-223,I0008页

作者： Qingyun Hu Wei Zhan Yifei Guo Laiming Luo Ronghua Zhang Di Chen Xinwen Zhou college of Biological and pharmaceutical science China Three Gorges University

Pd-based nanocatalyst is a potential oxygen reduction oxidation(ORR)catalyst because of its high activity in alkaline medium and low cost.In this work,bimetallic Pd Au nanocatalysts are prepared by one-pot hydrothermal method using triblock pluronic copolymers,poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)(PEO19-PPO69-PEO19)(P123)as reducer and stabilizer,and heat-treatment method is applied to regulate catalyst structure and improve catalyst activity.The results show that the heat treatment can agglomerate the catalyst to a certain extent,but effectively improve the crystallinity and alloying degree of the catalyst.The ORR performance of the Pd Au nanocatalysts obtained under different heat treatment conditions is systematically investigated.Compared with commercial Pd black and Pd Au catalyst before heat treatment,the ORR performance of Au Pd nanocatalyst obtained after heat treatment for one hour at 500℃ has been enhanced.The Pd Au nanocatalysts after heat treatment also display enhanced anti-methanol toxicity ability in acidic medium.

关键词： PdAu catalysts Nanochain Heat treatment Oxygen reduction reaction Anti-methanol oxidation

Ni nanoparticles confined by yolk-shell structure of CNT-mesoporous carbon for electrocatalytic conversion of CO_(2): Switching CO to formate

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Journal of Energy Chemistry 2022年第7期31卷 224-229,I0006页

作者： Juan Du Aibing Chen college of Chemical and pharmaceutical Engineering Hebei University of Science and TechnologyShijiazhuang 050018HebeiChina

Electrochemical reduction of CO_(2)(CO_(2)ER) to formate has been a promising route to produce value-added chemicals.Developing low-cost and efficient electrocatalysts with high product selectivity is still a grand challenge.Herein,a novel Ni nanoparticles-anchored CNT coated by mesoporous carbon with yolk-shell structure (CNT/Ni@mC) catalysis was designed for CO_(2)ER.Ni nanoparticles were confined in the cavity between CNT and mesoporous carbon shell and the confined space can be controlled by tuning the amount of silica precursor.The mesoporous carbon shell and confined space are beneficial to charge transmission during CO_(2)ER.In contrast to previous studies,the CNT/Ni@mC catalyst presents selectivity toward formate rather than CO.Electrochemical in situ attenuated total reflection Fourier transform infrared spectroscopy measurements indicate the presence of a COO* intermediate that converts to formate under CO_(2)ER conditions.The well-defined structural feature of the confined space of the Ni-based catalyst for selective CO_(2)ER to formate may facilitate in-depth mechanistic understandings on structural factors that affect CO_(2)ER performance.

关键词： Carbon dioxide electrochemical reduction Nickel-based catalyst Formate Yolk-shell CNT