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Paclitaxel-lipid prodrug liposomes for improved drug delivery and breast carcinoma therapy

Chinese Chemical Letters 2024年第2期35卷 335-340页

作者： Xin Wu Xinmei Chen Xinyu Wang haisheng he Jianming Chen Wei Wu Key Laboratory of Smart Drug Delivery of MOE School of PharmacyFudan UniversityShanghai 201203China Department of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Shanghai Wei Er Lab Shanghai 201707China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor *** are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’tolerance owing to excellent biocompatibility and ***,poor compatibility between PTX and liposomes compromises the stability,drug loading and anti-tumor capacity of liposomal *** address this issue,three lipids with various chain lengths,namely,myristic acid(MA,14C),palmitic acid(PA,16C)and stearic acid(SA,18C),were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes,*** liposomes show high stability and drug loadings,as well as sustained drug *** chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates,which further impact the pharmacokinetics,tumor accumulation,and anti-tumor efficacy of liposomal *** rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of *** all liposomes,PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo,owing to its moderate drug release and enzymatic conversion *** its superior safety,PTX-PA liposomes hold potential for further clinical translation.

关键词： Paclitaxel Lipids Prodrugs Liposomes Drug release Chemotherapy

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β-Lactoglobulin stabilized lipid nanoparticles enhance oral absorption of insulin by slowing down lipolysis

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Chinese Chemical Letters 2024年第4期35卷 287-291页

作者： Lu Li Suticha Chunta Xianzi Zheng haisheng he Wei Wu Yi Lu School of Pharmacy&Key Laboratory of Smart Drug Delivery of MOE Fudan UniversityShanghai 201203China Department of Clinical Chemistry Faculty of Medical TechnologyPrince of Songkla UniversitySongkhla 90110Thailand Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200433China Fudan Zhangjiang Institute Shanghai 201203China

Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, including nanoemulsions(NE@β-lg) and nanocapsules(NC@β-lg), were developed to enhance the oral absorption of insulin by slowing down lipolysis due to the protection from β-lg. Cremophor EL stabilized nanoemulsions(NE@Cre-EL) were prepared and set as a control. The lipid nanoparticles produced mild and sustained hypoglycemic effects, amounting to oral bioavailability of 3.0% ± 0.3%, 7.0% ± 1.1%, and7.7% ± 0.8% for NE@Cre-EL, NE@β-lg, and NC@β-lg, respectively. Aggregation-caused quenching(ACQ)probes enabled the identification of intact nanoparticles, which were used to investigate the in vivo and intracellular fates of the lipid nanoparticles. In vitro digestion/lipolysis and ex vivo imaging confirmed delayed lipolysis from β-lg stabilized lipid nanoparticles. NC@β-lg was more resistant to intestinal lipolysis than NE@β-lg due to the Ca^(2+)-induced crosslinking. Live imaging revealed the transepithelial transport of intact nanoparticles and their accumulation in the liver. Cellular studies confirmed the uptake of intact nanoparticles. Slowing down lipolysis via food proteins represents a good strategy to enhance the oral absorption of lipid nanoparticles and thus co-formulated biomacromolecules.

关键词： β-Lactoglobulin Lipid nanoparticles Oral absorption Insulin Lipolysis Aggregation-caused quenching

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Julolidinyl aza-BODIPYs as NIR-Ⅱ fluorophores for the bioimaging of nanocarriers

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3155-3168页

作者： Chang Liu Yifan Cai Zichen Zhang Yi Lu Quangang Zhu haisheng he Zhongjian Chen Weili Zhao Wei Wu Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China Key Laboratory of Smart Drug Delivery of MOE School of PharmacyFudan UniversityShanghai 201203China Department of MediChinal Chemistry School of PharmacyFudan UniversityShanghai 201203China

The aggregation-caused quenching(ACQ)rationale has been employed to improve the fluorescence imaging accuracy of nanocarriers by precluding free probe-derived ***,its usefulness is undermined by limited penetration and low spatiotemporal resolution of NIR-Ⅰ(700-900 nm)bioimaging owing to absorption and diffraction by biological tissues and tissue-derived *** study aimed to develop ACQ-based NIR-Ⅱ(1000-1700 nm)probes to further improve the imaging resolution and *** strategy employed is to install highly planar and electron-rich julolidine into the 3,5-position of aza-BODIPY based on the larger substituent *** newly developed probes displayed remarkable photophysical properties,with intense absorption centered at approximately 850 nm and bright emission in the 950-1300 nm *** with the NIR-Ⅰ counterpart P2,the NIR-Ⅱ probes demonstrated superior water sensitivity and quenching ***1 and ACQ6 exhibited more promising ACQ effects with absolute fluorescence quenching at water fractions above 40% and higher quenching stability with less than 2.0% fluorescence reillumination in plasma after 24 h of *** calculations verified that molecular planarity is more important than hydrophobicity for ACQ ***,in vivo and ex vivo reillumination studies revealed less than 2.5% signal interference from prequenched ACQ1,in contrast to 15% for P2.

关键词： 3,5-Julolidinyl Aza-BODIPY Nanocarriers Near-infrared Ⅱ Fluorescence imaging Aggregation-caused quenching Polymeric micelles Polymeric nanoparticles

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Ionic liquid-based in situ dynamically self-assembled cationic lipid nanocomplexes(CLNs)for enhanced intranasal siRNA delivery

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Chinese Chemical Letters 2024年第7期35卷 367-371页

作者： Luyu Zhang Zirong Dong Shuai Yu Guangyue Li Weiwen Kong Wenjuan Liu haisheng he Yi Lu Wei Wu Jianping Qi Key Laboratory of Smart Drug Delivery of MOE School of PharmacyFudan UniversityShanghai 201203China School of Pharmacy Shandong Academy of SciencesQilu University of TechnologyJi'nan 250353China College of Chemical Engineering North China University of Science and TechnologyTangshan 063210China

This research aims to develop a non-invasive strategy for small interfering RNA(siRNA)nasal delivery based on ionic liquids(ILs)and cationic lipid(2,3-dioleoyloxy-propyl)-trimethylammonium-chloride(DOTAP).Other than the classical role of penetration enhancer,ILs also acted as superior solvents to simultaneously load siRNA and DOTAP,forming siRNA-DOTAP-ILs(siRNA-DILs)*** nasal mucosa penetration,DOTAP and ILs components self-assembled into cationic lipid nanocomplexes to load siRNA for enhanced in situ *** siRNA-DILs demonstrated resistance against RNase,significant mucosa penetration,prolonged nasal retention,and satisfying gene-silencing efficacy at lower ***,DILs were also able to deliver KCa3.1-targeted siRNA effectively for the treatment of allergic rhinitis in rat model by nasal ***,DILs have great potentials to deliver biological macromolecules across nasal mucosa by in situ dynamic self-assembly.

关键词： Ionic liquids Cationic lipids Lipid nanoparticles siRNA Allergic rhinitis

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Rod-like mesoporous silica nanoparticles facilitate oral drug delivery via enhanced permeation and retention effect in mucus

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Nano Research 2022年第10期15卷 9243-9252页

作者： Wenjuan Liu Luyu Zhang Zirong Dong Kaiheng Liu haisheng he Yi Lu Wei Wu Jianping Qi School of Pharmacy Key Laboratory of Smart Drug Delivery of MOEFudan UniversityShanghai 201203China

The physiochemical characteristics of nanoparticles affect their in vitro and in vivo performance significantly,such as diameter,surface chemistry,and *** paper disclosed the effect of enhanced permeation and retention(EPR)in mucus caused by nanoparticle shape on improving oral *** spherical and rod-like mesoporous silica nanoparticles(MSNs)were used to evaluate shape effect of EPR in *** was loaded in MSNs as model *** in vitro release of fenofibrate from MSNs was dependent on nanoparticle shapes,but faster than that of raw *** drug release slowed down with the increase of aspect ratio due to longer channels in rod-like MSNs with higher aspect ***,in vivo study showed that the oral bioavailability of fenofibrate was the highest after loading in rod-like MSNs with aspect ratio of *** in vitro study of mechanisms revealed that superior mucus diffusion ability of rod-like MSNs with aspect ratio of 5 was conductive to higher ***,more rod-like MSNs with higher aspect ratio were able to diffuse into mucus and reside there compared to spherical and short counterparts,which demonstrated higher aspect ratio was beneficial to EPR effect of nanoparticles in *** study provides significant implication in rational oral drug carrier design.

关键词： mesoporous silica nanoparticles shape effect fenofibrate mucus layer enhanced permeation and retention effect

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基于城市信息模型(CIM)的未来城市场景迭代——以数字产城CIM平台为例

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新型工业化 2024年第3期14卷 23-31页

作者：何海生石琦李蓉张龙邢广良软通动力信息技术(集团)股份有限公司北京100193

城市信息模型(City Information Modeling,CIM)的兴起和广泛应用为城市高质量发展和智慧城市建设提供了重要支撑。本文面向智慧城市规建管需求,构建基于CIM的集“规划—投资—设计—建设—管理—运营—双碳—元宇宙”八大功能于一体的... 详细信息

城市信息模型(City Information Modeling,CIM)的兴起和广泛应用为城市高质量发展和智慧城市建设提供了重要支撑。本文面向智慧城市规建管需求,构建基于CIM的集“规划—投资—设计—建设—管理—运营—双碳—元宇宙”八大功能于一体的产城管理平台,实现线下物理城市与线上数字城市的深度融合,助力产城科学规划、高效建设和优质运营。在此基础上解析CIM平台的自我学习过程,提出数据迭代-模型迭代-服务迭代的多层次未来城市场景迭代框架,并分析其场景应用与反馈机制,助力产城全场景穿透,提高政府管理软实力。

关键词：数字产城 CIM 智慧城市场景迭代反馈机制

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树种重要值、树种多样性和土壤理化性质对土壤氨基糖的影响

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浙江农林大学学报 2024年第4期41卷 778-786页

作者：黄海燕唐慧敏金鹭施宇宋晓倩陈嘉琦贺海升张衷华唐中华东北林业大学化学化工与资源利用学院黑龙江哈尔滨150040 东北林业大学森林植物生态学教育部重点实验室黑龙江哈尔滨150040 东北林业大学林业生物制剂教育部工程研究中心黑龙江哈尔滨150040 东北林业大学黑龙江省林源活性物质生态利用重点实验室黑龙江哈尔滨150040 沈阳师范大学实验教学中心辽宁沈阳110000

【目的】土壤氨基糖是土壤微生物死亡残体的特异性标志物,对土壤碳、氮固存有重要作用。探究树种多样性和优势树种重要值对土壤氨基糖的影响机制。【方法】以东北林业大学实验林场为研究样地,采取0~20 cm的表层土壤,测定土壤葡萄糖(Glu... 详细信息

【目的】土壤氨基糖是土壤微生物死亡残体的特异性标志物,对土壤碳、氮固存有重要作用。探究树种多样性和优势树种重要值对土壤氨基糖的影响机制。【方法】以东北林业大学实验林场为研究样地,采取0~20 cm的表层土壤,测定土壤葡萄糖(Glu)、土壤半乳糖(Gal)、土壤胞壁酸(Mur)及土壤总氨基糖(TA)质量分数,计算样地内树种多样性指数和优势树种重要值,通过相关分析、冗余分析、方差分解分析研究确定影响土壤氨基糖的主要因素及其贡献程度。【结果】(1)土壤葡萄糖、土壤半乳糖、土壤胞壁酸、土壤总氨基糖质量分数与土壤全氮质量分数、土壤电导率和土壤有机碳质量分数显著正相关(Phellodendron amurense、金银忍冬Lonicera maackii、胡桃楸Juglans mandshurica重要值均显著正相关(P<0.05);土壤半乳糖、土壤胞壁酸、土壤总氨基糖质量分数与梣叶槭Acer negund重要值显著正相关(P<0.05)。冗余分析发现:黑皮油松、蒙古栎不利于氨基糖积累,而黄檗、梣叶槭、金银忍冬、胡桃楸有利于土壤氨基糖的积累。(3)方差分解分析表明:树种重要值对土壤氨基糖质量分数变化的贡献程度(35.4%)显著高于树种多样性(6.4%)和土壤理化性质(17.2%)。【结论】通过增加梣叶槭、金银忍冬、黄檗和胡桃楸等树种来为维持较高的树种多样性,能更好地促进人工林土壤氨基糖的积累,进而改善土壤碳氮固存能力。

关键词：树种多样性树种重要值土壤理化性质土壤氨基糖

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The long-circulating effect of pegylated nanoparticles revisited via simultaneous monitoring of both the drug payloads and nanocarriers

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2479-2493页

作者： Wufa Fan Haixia Peng Zhou Yu Luting Wang haisheng he Yuhua Ma Jianping Qi Yi Lu Wei Wu Key Laboratory of Smart Drug Delivery of MOE School of PharmacyFudan UniversityShanghai 201203China Center for Medical Research and Innovation Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province School of PharmacyQinghai Nationalities UniversityXining 810007China

The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin(DOX)-loaded methoxy polyethylene glycol-polycaprolactone(mPEG-PCL) nanoparticles. Comparison of the kinetic profiles of both DOX and nanocarriers verifies the long-circulating effect, though of limited degree, as a result of pegylation. The nanocarrier profiles display fast clearance from the blood despite dense PEG decoration;DOX is cleared faster than the nanocarriers. The nanocarriers circulate longer than DOX in the blood, suggesting possible leakage of DOX from the nanocarriers. hepatic accumulation is the highest among all organs and tissues investigated, which however is reversely proportionate to blood circulation time. Pegylation and reduction in particle size prove to extend circulation of drug nanocarriers in the blood with simultaneous decrease in uptake by various organs of the mononuclear phagocytic system. It is concluded that the long-circulating effect of mPEG-PCL nanoparticles is reconfirmed by monitoring of either DOX or the nanocarriers, but the faster clearance of DOX suggests possible leakage of a fraction of the payloads. The findings of this study are of potential translational significance in design of nanocarriers towards optimization of both therapeutic and toxic effects.

关键词： Long-circulating In vivo fate Aggregation-caused quenching Nanoparticles mPEG-PCL Doxorubicin Drug delivery Pharmacokinetics

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Accurate and sensitive probing of onset of micellization based on absolute aggregation-caused quenching effect

Aggregate

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Aggregate 2022年第5期3卷 172-184页

作者： haisheng he Chang Liu Jiang Ming Yongjiu Lv Jianping Qi Yi Lu Xiaochun Dong Weili Zhao Wei Wu Key Laboratory of Smart Drug Delivery of MOE School of PharmacyFudan UniversityShanghaiChina Department of Chemistry Fudan UniversityShanghaiChina Shanghai Skin Disease Hospital Tongji University School of MedicineShanghaiChina Center for Medical Research and Innovation Shanghai Pudong HospitalPudong Medical CenterFudan UniversityShanghaiChina

Probing the onset of micellization,or determining the critical micelle concentration(CMC),is of crucial importance while remains to be challenged by growing demand for extraordinary sensitivity and *** fluorometry has attracted wide attention owing to its superiority in simplicity and sensitivity over other methods,the presence and fluctuation of background fluorescence of conventional fluorescent probes undermine the accuracy of CMC ***,a series of novel fluorescent probes without background fluorescence at a concentration below CMC owing to absolute aggregation-caused quenching(aACQ)are utilized for sensitive and accurate measurement of *** aACQ probes aggregate spontaneously and instantly in an aqueous environment owing to molecular π-π stacking with fluorescence quenching ***,the absence of background fluorescence at a concentration below CMC clears relevant interference associated with conventional *** this study,the new method is applied for versatile surfactants with CMCs ranging from nanomolar to millimolar concentrations,especially copolymers with ultralow *** higher sensitivity and accuracy are highlighted by comparison with conventional probes.

关键词： aggregation-caused quenching amphiphile copolymer critical micelle concentration critical micelle temperature fluorometry

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四维斑点追踪显像评价高血压对糖尿病患者左心房功能影响的研究

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心电与循环 2024年第3期43卷 266-270页

作者：高继康陈晓冰黄文凡张雨濛马芳花何海生杭州市临平区第一人民医院(浙江大学医学院附属第二医院临平院区)超声科 311100 杭州市临平区第一人民医院(浙江大学医学院附属第二医院临平院区)内分泌科 311100

目的探讨四维斑点追踪显像(4D-STI)评价高血压对糖尿病患者左心房功能的影响。方法回顾性选择2021年1月至12月杭州市临平区第一人民医院收治入院的2型糖尿病患者95例,合并高血压(合并高血压组)57例,未合并高血压(未合并高血压组)38例,... 详细信息

目的探讨四维斑点追踪显像(4D-STI)评价高血压对糖尿病患者左心房功能的影响。方法回顾性选择2021年1月至12月杭州市临平区第一人民医院收治入院的2型糖尿病患者95例,合并高血压(合并高血压组)57例,未合并高血压(未合并高血压组)38例,健康体检者65人为对照组。采用4D-STI比较各组心室舒张末期左心房容积(LAVd)、心室收缩末期左心房容积(LAVs)、左心房射血前期容积(LAVp)、左心房每搏排血容积(LAEV)、左心房被动排血容积(LAPV)、左心房主动排血容积(LAAV)、左心房射血分数(LAEF)、左心房被动排血分数(LAPEF)、左心房主动排血分数(LAAEF),左心房储备期纵向应变(LALSr)、左心房储备期圆周应变(LACSr)、左心房管道期纵向应变(LALScd)、左心房管道期圆周应变(LACScd)、左心房收缩期纵向应变(LALSct)、左心房收缩期圆周应变(LACSct)。结果合并高血压组、未合并高血压组的LAVd、LAVp、LAAV高于对照组,LAPV、LAEF、LAPEF小于对照组,差异均有统计学意义(均P<0.05)。合并高血压组的LAVs高于对照组、未合并高血压组,LAVd、LAVp、LAAV高于未合并高血压组,LAEF、LAPEF小于未合并高血压组,差异均有统计学意义(均P<0.05)。3组对象的LALSr、LACSr、LALScd、LACScd比较差异均有统计学意义(均P<0.05),合并高血压组、未合并高血压组上述指标均低于对照组,差异均有统计学意义(均P<0.05)。结论利用4D-STI能够评价高血压对糖尿病患者左心房功能的影响。

关键词：四维斑点追踪显像糖尿病高血压左心房心功能

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