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Copper-mediated chemodynamic therapy with ultra-low copper consumption by doping cupric ion on cross-linked(R)-(+)-lipoic acid nanoparticles

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Regenerative Biomaterials 2023年第1期10卷 670-677页

作者： Rong Cui Bing Li Chunyan Liao shiyong zhang College of Biomedical Engineering National Engineering Research Center for BiomaterialsSichuan UniversityChengdu 610064China Hubei Key Laboratory of Wudang Local Chinese Medicine Research School of Pharmaceutical SciencesHubei University of MedicineShiyan 442000HubeiChina

Cu-mediated chemodynamic therapy(CDT)has attracted prominent attention owing to its advantages of pH independence and high efficiency comparing to Fe-mediated CDT,while the application of Cu-based CDT agents was impeded due to the high copper consumption caused by the metabolism loss of copper and the resultant potential ***,we developed a new copper-mediated CDT agent with extremely low Cu usage by anchoring copper on cross-linked lipoic acid nanoparticles(Cu@cLAs).After endocytosis into tumor cells,the Cu@cLAs were dissociated into LA and dihydrolipoic acid(DHLA)(reduced form of LA)and released Cu^(2+)and Cu+(oxidized form of Cu^(2+)),the two redox couples recycled each other in cells to achieve the efficient killing of cancer cells by delaying metabolic loss and increasing the ROS level of tumor *** self-recycling was confirmed in cells by the sustained high Cu/DHLA content and persistent ROS generation *** antitumor study based on the MCF-7/R nude mice gave the Cu@cLAs a tumor inhibitory rate up to 77.9%at the copper of 0.05 mg kg^(−1),the first dosage reported so far lower than that of normal serum copper(0.83±0.21 mg kg^(−1)).This work provides not only a new promising clinical strategy for the copper excessive use in copper-mediated CDT,but also gives a clue for other metal mediated disease therapies with the high metal consumption.

关键词： chemodynamic therapy copper metabolism (R)-(+)-lipoic acid nanodrug

Cross-linked lipoic acid nanocapsules serve as H_(2)O_(2) amplifier to strengthen the H_(2)O_(2)-sensitive prodrug activation

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Science China Chemistry 2023年第9期66卷 2654-2663页

作者： Jiangbing Tan Pei Jing Xiao Xiao Yulong Liao Chunyan Liao shiyong zhang College of Biomedical Engineering and National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China Department of Pharmacy the Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

The H_(2)O_(2) -triggered prodrug activation represents a hot topic while the low H_(2)O_(2) level of cancer cells hindered the complete activation of parent drugs and resulted in the poor therapeutic effect. Here, we developed an H_(2)O_(2) amplifier fabricated by crosslinked lipoic acid nanocapsules(cLANCs), which would selectively elevate the intracellular H_(2)O_(2) level of cancer cells 3.4-fold higher than that of untreated cancer cells so as to speed up the activation of parent drug from the loaded prodrugs(Pro-5-FU). The cytotoxicity showed that the killing effect of Pro-5-FU loaded in cLANCs(Pro-5-FU@cLANCs) arrived up to 1.6-time higher than that of Pro-5-FU alone against A549 cells, and was even close to free 5-FU. The in vivo anticancer evaluation gave the tumor inhibition rate(TIR) and survival rate(SR) of Pro-5-FU@cLANCs against A549 tumor-bearing nude mice up to 73.1% and 80%,respectively, much higher than those of Pro-5-FU(TIR: 41.2%, SR: 20%) or free 5-FU(TIR: 50.6%, SR: 0%). This nanodrug constructed the first example that utilizes the drug carriers as H_(2)O_(2) amplifier to strengthen the prodrug activation.

关键词： cancer therapy prodrug activation H_(2)O_(2)amplifier drug carrier

Biodegradable polymeric nanoparticles based on amphiphilic principle:construction and application in drug delivery

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Science China Chemistry 2014年第4期57卷 461-475页

作者： zhang shiyong WU Yao HE Bin LUO Kui GU ZhongWei National Engineering Research Center for Biomaterials Sichuan University

The use of nanotechnology in drug-delivery systems(DDS) is attractive for advanced diagnosis and treatment of cancer diseases. Biodegradable polymeric nanoparticles, for example, have promising applications as advanced drug carriers in cancer treatment. In this review, we discuss the development of drug-delivery systems based on an amphiphilic principle mainly conducted by our group for anti-cancer drug delivery. We first briefly address the synthetic chemistry for amphiphilic biodegradable polymers. In the second part, we summarize progress in the application of self-assembled polymer micelles using amphiphilic biodegradable copolymers as anti-tumor drug carriers.

关键词： biodegradable polymer miceUe amphiphilicity drug-delivery system cancer

Flooding attack and defence in Ad hoc networks

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Journal of Systems Engineering and Electronics 2006年第2期17卷 410-416页

作者： Yi Ping Hou Yafei Zhong Yiping zhang shiyong Dai Zhoulin School of Information Security Engineering Shanghai Jiaotong Univ. Shanghai 200030 P. R. China Dept. of Computing and Information Technology Fudan Univ. Shanghai 200433 P. R. China Graduate School of Engineering Kochi University of Technology Rochi 782-8502 Japan.

Mobile ad hoc networks are particularly vulnerable to denial of service （DOS） attacks launched through compromised nodes or intruders. In this paper, we present a new DOS attack and its defense in ad hoc networks. The new DOS attack, called AA hoc Flooding Attack（AHFA）, is that intruder broadcasts mass Route Request packets to exhaust the communication bandwidth and node resource so that the valid communication can not be kept. After analyzed AM hoc Flooding Attack, we develop Flooding Attack Prevention （FAP）, a genetic defense against the AM hoc Flooding Attack. When the intruder broadcasts exceeding packets of Route Request, the immediate neighbors of the intruder record the rate of Route Request. Once the threshold is exceeded, nodes deny any future request packets from the intruder. The results of our implementation show FAP can prevent the AM hoe Flooding attack efficiently.

关键词： computer networks security mobile Ad hoe networks routing protocol denial of service Ad hoc flooding attack.

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光响应纳米材料在骨组织再生中的应用

中国组织工程研究 2025年第16期29卷 3469-3475页

作者：冯淑琦张诗咏姚珂奕唐渝菲王锴周雪梅向琳口腔疾病防治全国重点实验室国家口腔医学中心国家口腔疾病临床医学研究中心四川大学华西口腔医院四川省成都市610041 四川大学化学工程学院四川省成都市610065

背景:光响应纳米材料兼具纳米材料的优点以及光响应的独特优势,在组织再生、生物成像、疾病诊断、药物递送和靶向治疗等生物医学领域广泛应用,是目前功能材料领域的研究热点。目的:综述光响应纳米材料及其在骨组织再生中的应用优势和研... 详细信息

背景:光响应纳米材料兼具纳米材料的优点以及光响应的独特优势,在组织再生、生物成像、疾病诊断、药物递送和靶向治疗等生物医学领域广泛应用,是目前功能材料领域的研究热点。目的:综述光响应纳米材料及其在骨组织再生中的应用优势和研究进展。方法:应用计算机检索中国知网和PubMed数据库,主要的英文检索词为“light-responsive,photoresponsive,nanomaterials,bone defect,bone regeneration,osteogenesis,osseointegration”,主要的中文检索词为“光响应,纳米材料,骨缺损,骨再生,骨结合”,根据纳入和排除标准筛选相关文献,最终纳入59篇文献进行综述。结果与结论:光响应纳米材料的表面形貌可通过直接调节成骨细胞及间接调节免疫相关细胞的基因表达及生物学行为来促进骨组织再生。光响应纳米材料可利用光热抗菌、光动力抗菌促进感染性骨缺损的修复。光响应纳米材料产生的温和光热刺激可通过上调成骨相关基因、蛋白质的表达及功能性成骨来有效增强成骨作用。光响应纳米材料在光照下可产生电子,进而通过调节细胞局部电位变化达到无创促进骨组织再生的目的。基于光响应纳米材料的药物释放系统可在特定光源照射下发生结构变化,以促进药物释放,为骨组织再生提供靶向治疗策略。

关键词：光响应纳米材料骨缺损骨再生骨结合综述

Co-solvent polarity controlled self-assembly of tetraphenylethylene-buried amphiphile for size-regulated tumor accumulation

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Regenerative Biomaterials 2018年第5期5卷 275-282页

作者： Jingsheng Huang Yun Chen Pengxiang Zhao Yunlong Yu shiyong zhang Zhongwei Gu National Engineering Research Center for Biomaterials Sichuan University29 Wangjiang RoadChengdu 610064China Science and Technology on Surface Physics and Chemistry Laboratory Mianyang 621907China College of Materials Science and Engineering Nanjing Tech UniversityNanjingJiangsu 210009China

We report that the co-solvent polarity can precisely control the TPE-buried amphiphile 1 to selfassemble into nanoparticles(NPs)in water with size range from21–32nm to 55–68nm to 95–106 *** for size,these TPE-buried amphiphile fabricated NPs hold identical physical properties such as spherical shape,surface charge,and luminescent properties,and moreover,after covalent capture of the acrylate hydrophilic heads,the resulting cross-linked NPs(cNPs I–III)own excellent in vivo stability,which thus would be an ideal platform for investigating the size effects on tumor accumulation and penetration.

关键词： polarity control aggregation-induced emission size regulation tumor accumulation

Azobenzene quaternary ammonium salt for photo-controlled and reusable disinfection without drug resistance

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Chinese Chemical Letters 2023年第2期34卷 440-445页

作者： Yuhong Zhu Pengfei Li Caikun Liu Mengqi Jia Yadong Luo Dengfeng He Chunyan Liao shiyong zhang College of Chemistry Sichuan UniversityChengdu 610064China College of Biomedical Engineering and National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China

The abuse of antibiotics causes severe bacterial resistance, and the shortage of antibiotics has created a global public health crisis. This situation has prompted people to develop new antibacterial agents independent of traditional antibiotics. Here, we created a series of photosensitive azobenzene-quaternary ammonium salt smart antibacterial agents by connecting azobenzene with amines with different chain lengths to improve the antibacterial selectivity of quaternary ammonium salt(QAS) and prevent the accumulation of active QAS in the environment. After trans-cis isomerization, the solubility of the title compound(compound 4) increased and the antibacterial property enhanced. The experimental results suggested that the antibacterial effect of compound 4 was significantly enhanced after 365 nm light irradiation, and it had photosensitive intelligent antibacterial activity and could be reused. Notably, we did not obtain any mutants of Staphylococcus aureus or Escherichia coli resistant to compound 4. In general,compound 4 has the advantages of high yield, photo-controllable antibacterial properties, reusability, and does not induce bacterial resistance. This photosensitive antibacterial compound provides a new idea for the construction of intelligent disinfectants and is expected to be a candidate for disinfectants in public facilities and medical architecture.

关键词： Azobenzene Quaternary ammonium salt Photosensitivity Repeatability Antibacterial agent

Yushu earthquake synergic analysis using multimodal SAR datasets

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Chinese Science Bulletin 2010年第31期55卷 3499-3503页

作者： GUO HuaDong WANG XinYuan LI XinWu LIU Guang zhang Lu YAN shiyong Key Laboratory of Digital Earth Center for Earth Observation and Digital Earth Chinese Academy of Sciences Beijing 100190 China

The large earthquake measuring 7.1 on the Richter scale that occurred in Yushu County,Qinghai Province,China,on April 14,2010,caused a huge loss of life and major damage to people's *** three modal synthetic-aperture radar(SAR) datasets,wide-swath SAR,interferometric SAR and polarimetric SAR,the following studies were conducted:(1) From Radarsat-2 wide swath SAR data,the regional geological structures and lithologic distribution characteristics of the Yushu earthquake were analyzed.(2) Using advanced land observing satellite/phased array L-band interferometric SAR data,the coseismic deformation field of the Yushu earthquake was obtained,and the size and spatial distribution of deformation were studied combining with the result of regional geological background analysis.(3) From Radarsat-2 polarimetric SAR data,the H-α-ρ method was used to extract the spatial distribution of building collapse caused by the earthquake in the Yushu urban area,and the reasons for the severe earthquake damage to buildings are also discussed and *** study results demonstrate the effectiveness and important potential of using multimodal SAR data for synergic analysis and assessment of earthquake disasters.

关键词：地震台网协同分析玉树县数据集多式联运特区合成孔径雷达区域地质构造

Overexpression of OsPIL15, a phytochrome-interacting factor-like protein gene, represses etiolated seedling growth in rice

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Journal of Integrative Plant Biology 2014年第4期56卷 373-387页

作者： Jinjun Zhou Qianqian Liu Fang zhang Yingying Wang shiyong zhang Huimin Cheng Lihua Yan Li Li Fan Chen Xianzhi Xie Shandong Rice Research Institute Shandong Academy of Agricultural Sciences Shandong Provincial Key Laboratory of Crop Genetic Improvement Ecology and Physiology College of Life Sciences Shandong Normal University Institute of Genetics and Developmental Biology the Chinese Academy of Sciences

Phytochrome-interacting factors （PIFs） regulate an array of developmental responses ranging from seed germi- nation to vegetational architecture in Arabidopsis. However, information regarding the functions of the PIF family in monocots has not been widely reported. Here, we investigate the roles of OsPIL15, a member of the rice （Oryza sativa L. cv. Nipponbare） PIF family, in regulating seedling growth. OsPIL15 encodes a basic helix-loop-helix factor localized in the nucleus. OsPIL15-OX seedlings exhibit an exaggerated shorter above- ground part and undeveloped root system relative to wild-type seedlings, suggesting that OsPIL15 represses seedling growth in the dark. Microarray analysis combined with gene ontology analysis revealed that OsPIL15 represses a set of genes involved in auxin pathways and cell wall organization or biogenesis. Given the important roles of the auxin pathway and cell wall properties in controlling plant growth, we speculate that OsPIL15 represses seedling growth likely by regulating the auxin pathway and suppressing cell wall organization in etiolated rice seedlings. Additionally, exposure to red light or far-red light relieved growth retardation and promoted seedling elongation in the OsPIL15-OX lines, despite higher levels of OsPIL15 transcripts under red light and far-red light than in the dark. These results suggest that light regulation of OsPIL15 expres- sion is probably involved in photomorphogenesis in rice.

关键词： Auxin cell wall etiolated seedling rice photomorpho-genesis phytochrome-interacting factor