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Engineering W/O/W pickering emulsion for the enhanced antigen delivery and immune responses

Particuology 2024年第9期92卷 224-233页

作者： Sihua Wu xiaonan Huang Yin Ma Naoki Asakawa yufei xia State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100081China Key Laboratory of Biopharmaceutical Preparation and Delivery Chinese Academy of SciencesBeijing100190China Division of Molecular Science Graduate School of Science and TechnologyGunma University1-5-1Tenjin-choKiryu376-8515Japan Sinovac Biotech Ltd. Beijing100085China School of Chemical Engineering Nanjing Tech UniversityNanjing211816China School of Chemical Engineering University of Chinese Academy of SciencesBeijing100049China

Tumor immunotherapy,particularly cancer vaccines,holds promise for combating cancer by harnessing tailored immune responses against malignant ***,conventional approaches face challenges in efficiently delivering antigens for optimal immune *** adjuvants,like MF59,enhance cellular uptake but struggle to induce robust CD8^(+)T cell ***,we introduce a novel strategy employing a water-in-oil-in-water(W/O/W)multiple Pickering emulsion(mPE)for antigen *** mPE,utilizing biocompatible,pH-sensitive particles,encapsulates antigens within the inner water phase,ensuring enhanced intracellular processing and dictating the intracellular fate of antigens for improved *** vitro and in vivo studies demonstrated that mPEs induced robust dendritic cells activation and antigen cross-presentation,leading to a significantly enhanced immune ***,calcium phosphate-stabilized mPE(CaP-mPE)illustrated the more robust IFN-γ^(+)T cell *** comparison with traditional surfactant-stabilized multiple emulsions,CaP-mPE significantly inhibit tumor growth and effectively prolong the survival of tumor-bearing *** innovative approach offers a promising avenue for the development of effective cancer vaccines with potent cellular immune responses.

关键词： Cancer vaccine Multiple pickeringemulsion Adjuvant Antigen delivery Anti-tumor response

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Pickering emulsion transport in skeletal muscle tissue:A dissipative particle dynamics simulation approach

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Chinese Journal of Chemical Engineering 2024年第4期68卷 65-75页

作者： Xuwei Liu Wei Chen yufei xia Guanghui Ma Reiji Noda Wei Ge State Key Laboratory of Mesoscience and Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China Division of Environmental Engineering Science Graduate School of Science and TechnologyGunma University1-5-1 Tenjin-choKiryuGunma 376-8515Japan State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China

Lymph node targeting is a commonly used strategy for particulate vaccines,particularly for Pickering ***,extensive research on the internal delivery mechanisms of these emulsions,especially the complex intercellular interactions of deformable Pickering emulsions,has been surprisingly *** gap in knowledge holds significant potential for enhancing vaccine *** study aims to address this by summarizing the process of lymph-node-targeting transport and introducing a dissipative particle dynamics simulation method to evaluate the dynamic processes within cell *** transport of Pickering emulsions in skeletal muscle tissue is specifically investigated as a case *** factors impacting the transport process are explored,including local cellular tissue environmental factors and the properties of the Pickering emulsion *** simulation results primarily demonstrate that an increase in radial repulsive interaction between emulsion particles can decrease the transport ***,larger intercellular gaps also diminish the transport efficiency of emulsion droplet particles due to the increased motion complexity within the intricate transport space compared to a single *** study sheds light on the nuanced interplay between engineered and biological systems influencing the transport dynamics of Pickering *** insights hold valuable potential for optimizing transport processes in practical biomedical applications such as drug ***,the desired transport efficiency varies depending on the specific *** instance,while a more rapid transport might be crucial for lymph-node-targeted drug delivery,certain applications requiring a slower release of active components could benefit from the reduced transport efficiency observed with increased particle repulsion or larger intercellular gaps.

关键词： Pickering emulsion Skeletal muscular cells Transport phenomena Dissipative particle dynamics Drug delivery

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至真方固体双向发酵工艺的建立及其药效评价

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中药新药与临床药理 2024年第7期35卷 1061-1068页

作者：夏宇飞王松坡刘忠上海交通大学药学院上海200240 上海交通大学医学院附属第一人民医院上海200080

目的以中药固体双向发酵方法,建立至真方的新型发酵工艺。方法①通过文献研究拟定候选发酵菌种。对候选发酵菌种进行平板混合实验,考察各菌种间生长兼容性。采用CCK-8细胞增殖抑制实验,比较不同发酵条件下所得产物对人结直肠癌细胞(HCT... 详细信息

目的以中药固体双向发酵方法,建立至真方的新型发酵工艺。方法①通过文献研究拟定候选发酵菌种。对候选发酵菌种进行平板混合实验,考察各菌种间生长兼容性。采用CCK-8细胞增殖抑制实验,比较不同发酵条件下所得产物对人结直肠癌细胞(HCT-8)的半数抑制浓度(IC50),评判发酵体系的优劣,从而确定发酵菌种、发酵时长等关键发酵参数,建立发酵工艺。②通过HCT-8细胞增殖抑制率,以及巨噬细胞(RAW264.7)NO释放率和吞噬活性测定,比较至真方发酵前后的体外药效差异。结果黑曲霉和酵母菌为最优发酵菌种组合,4 d为最优发酵时长。在此发酵条件下,发酵组对HCT-8细胞的IC50为67.41μg·mL^(-1),生药组对HCT-8细胞的IC50为1032μg·mL^(-1);与生药组比较,发酵组能显著抑制RAW264.7释放炎症因子NO,并显著提升其吞噬活性。结论该研究建立了至真方固体双向发酵新工艺。在该发酵体系下,至真方的体外抗结直肠癌活性、抗炎活性和促免疫活性得到显著提升。

关键词：至真方发酵工艺固体双向发酵抗癌活性抗炎活性促免疫活性

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Optimising the oil phases of aluminium hydrogel-stabilised emulsions for stable,safe and efficient vaccine adjuvant

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Frontiers of Chemical Science and Engineering 2022年第6期16卷 973-984页

作者： Lili Yuan xiao-Dong Gao yufei xia Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China

To increase antibody secretion and dose sparing,squalene-in-water aluminium hydrogel(alun^-stabilised emulsions(ASEs)have been developed,which offer increased surface areas and cellular interactions for higher antigen loading and enhanced immune ***,the squalene(oil)in previous attempts suffered from limited oxidation resistance,thus,safety and stability were *** a clinical translational perspective,it is imperative to screen the optimal oils for enhanced emulsion ***,because of the varying oleic to linoleic acid ratio,soybean oil,peanut oil,and olive oil were utilised as oil phases in the preparation of aluminium hydrogel-stabilised squalene-in-water emulsions,which were then screened for their stability and ***,the underlying mechanisms of oil phases and emulsion stability were unravelled,which showed that a higher oleic to linoleic acid ratio increased anti-oxidative capabilities but reduced the long-term storage stability owing to the relatively low zeta potential of the prepared *** a result,compared with squalene-in-water ASEs,soybean-in-water ASEs exhibited comparable immune responses and enhanced *** optimising the oil phase of the emulsion adjuvants,this work may offer an alternative strategy for safe,stable,and effective emulsion adjuvants.

关键词： pickering emulsion vaccine adjuvant alum-stabilised emulsion oleic to linoleic acid ratio stability

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Aggregating particles on the O/W interface:Tuning Pickering emulsion for the enhanced drug delivery systems

Aggregate

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Aggregate 2022年第2期3卷 3-21页

作者： Yali Ming yufei xia Guanghui Ma State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190P.R.China University of Chinese Academy of Sciences Beijing 100049P.R.China

The rational design of drug delivery systems has led to enhanced targeting,increased efficiency,and a reduction of side effects in chemotherapies and *** most biological reactions took place at the interface,particle-stabilized emulsion(Pickering emulsion),may offer major implications for the advanced drug loading,delivery,and controlled *** fact,it is the aggregating particles that determined the multi-level structure,multi-valent cellular interactions,and the multi-functional physiochemical properties in drug delivery.A deeper understanding on the tunable aggregating patterns and properties,as well as the underlying mechanisms,may pave the way for the efficient drug delivery,and also aided the progressing of“Aggregology”beyond molecules to particles,emulsions,and the biomedical ***,the recent development of Pickering emulsions and their applications in drug delivery were thoroughly *** to control over the physiochemical properties were illustrated based on particle properties,energy input,and the choices of continuous and dispersion *** particular,enough emphasis was attached on the structure-effect relationship between the tunable physiochemical properties and the delivery process,such as the multi-level structure for effective loading,flexibility and permeability for enhanced delivery,and the stimuli-responsiveness for the controlled *** channeling the unique interfacial properties and the enhanced drug delivery efficiency,this work may shed light on the rational design of Pickering emulsions for the efficient drug delivery.

关键词： drug delivery system multi-valent interactions particle aggregation Pickering emulsion softness

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Pickering emulsion transport in skeletal muscle tissue: A dissipative particle dynamics simulation approach

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中国化学工程学报（英文版） 2024年第4期 65页

作者： Xuwei Liu Wei Chen yufei xia Guanghui Ma Reiji Noda Wei Ge

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Molecular dynamics simulations of ovalbumin adsorption at squalene/water interface

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Chinese Journal of Chemical Engineering 2022年第10期50卷 369-378页

作者： Qingxia Xiong Ying Ren yufei xia Guanghui Ma Reiji Noda Wei Ge State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China Division of Environmental Engineering Science Graduate School of Science and TechnologyGunma University1-5-1 Tenjin-choKiryuGunma 376-8515Japan State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing 100190China

The adsorption of protein molecules to oil/water(O/W)interface is of critical importance for the product design in a wide range of technologies and industries such as biotechnology,food industry and pharmaceutical *** this work,with ovalbumin(OVA)as the model protein,the adsorption conformations at the O/W interface and the adsorption stability have been systematically studied via multiple simulation methods,including all-atom molecular dynamic(AAMD)simulations,coarse-grained molecular dynamic(CGMD)simulations and enhanced sampling *** computational results of AAMD and CGMD show that the hydrophobic tail of OVA tends to be folded under long time relaxation in aqueous phase,and multiple adsorption conformations can exist at the interface due to heterogeneous interactions raising from oil and water *** further study the adsorption sites of the protein,the adsorption kinetics of OVA at the O/W interface is simulated using metadynamics method combined with CGMD simulations,and the result suggests the existence of multiple adsorption conformations of OVA at interface with the head-on conformation as the most stable *** all,this work focuses on the adsorption behaviors of OVA at squalene/water interface,and provides a theoretical basis for further functionalization of the proteins in emulsion-based products and engineering.

关键词： Molecular dynamicssimulation Metadynamics Protein adsorption Structural stability Ovalbumin

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膳食纤维在超短肠综合征肠康复治疗中的作用研究

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中华临床营养杂志 2024年第4期32卷 217-225页

作者：齐欣夏宇飞刘思睿高学金章黎王新颖南京大学医学院附属金陵医院、普通外科研究所南京210002 东南大学医学院南京210009

目的探究膳食纤维在超短肠综合征肠康复治疗中的作用。方法研究纳入南京大学医学院附属医院普通外科2012年1月至2023年10月诊断为超短肠综合征的住院患者34例,根据其营养支持治疗期间是否行肠康复治疗分为三组:营养治疗组(11例)、生长激... 详细信息

目的探究膳食纤维在超短肠综合征肠康复治疗中的作用。方法研究纳入南京大学医学院附属医院普通外科2012年1月至2023年10月诊断为超短肠综合征的住院患者34例,根据其营养支持治疗期间是否行肠康复治疗分为三组:营养治疗组(11例)、生长激素+谷氨酰胺肠康复治疗组(10例)及生长激素+谷氨酰胺+膳食纤维肠康复治疗组(13例)。肠康复治疗组均采用重组人生长激素注射液0.05 mg/(kg·d),谷氨酰胺粉5 g/d。记录患者的治疗方案及其变化和治疗前后的血液学指标、营养指标、肠道吸收指标、粪便性状评分及生活质量评分等指标,分析不同治疗方案对患者临床结局的影响。结果与营养治疗组和生长激素+谷氨酰胺肠康复治疗组相比,生长激素+谷氨酰胺+膳食纤维肠康复治疗组的肠内营养液体增加量、肠外营养能量减少量、肠道湿吸收增加量、排便次数减少量及血红蛋白上升值等显著增加,差异有统计学意义(P<0.05);同时其治疗后胰岛素样生长因子-1及胰岛素样生长因子结合蛋白水平等营养状态相关指标明显升高(P<0.01)。结论营养支持联合肠康复治疗可以显著改善超短肠综合征患者营养状况及肠道吸收率等指标,在肠康复治疗方案中联合使用膳食纤维可使其获益更为显著。

关键词：超短肠综合征膳食纤维肠康复治疗

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血运重建治疗对伴慢性多血管病变的急性肠系膜缺血导致的短肠综合征患者肠康复治疗效果的影响

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中华普通外科杂志 2024年第3期39卷 172-182页

作者：夏宇飞齐欣朱旻怡高学金章黎孙羽东王新颖东南大学医学院南京210009 南京大学医学院附属金陵医院全军普通外科研究所南京210002

目的探索伴慢性多血管病变的急性肠系膜缺血(acute mesenteric ischemia,AMI)导致的短肠综合征(short bowel syndrome,SBS)患者在肠康复治疗(intestinal rehabilitation therapy,IRT)前接受血运重建治疗能否优化IRT的疗效。方法回顾性分析2012年1月至2023年10月期间在中国人民解放军东部战区总医院诊断由伴慢性多血管病变的AMI导致SBS并接受IRT的住院患者18例的临床资料。结果在IRT后,血运重建组的四肢骨骼肌指数和握力的增加量显著高于对照组,分别为[(0.28±0.26)kg/m^(2)比(0.02±0.21)kg/m^(2),P=0.033]和[(0.97±0.33)kg比(0.48±0.34)kg,P=0.007]。同样,血运重建组肠内营养(EN)摄入量的增加量显著高于对照组[(572.5±93.6)ml/d比(375.2±176.3)ml/d,P=0.012],并伴随着肠道氮吸收率更高的提升[(25.06±14.06)%比(13.84±4.62)%,P=0.034]和肠道症状评定量表评分更大幅度的降低[(-15.88±3.94)分比(-6.33±5.13)分,P=0.030],且两组EN制剂类型的组成在IRT后也有显著差异(P=0.046)。此外,血运重建组出院时的简明健康量表(SF-36)在躯体疼痛(BP)、总体健康(GH)、活力(VT)、社会功能(SF)、精神健康(MH)等五项指标的得分上显著高于对照组(P<0.05)。结论由伴慢性多血管病变的AMI导致SBS的患者接受血运重建治疗不能使其在IRT中获得体重和血液学营养指标上更高的增长,但有利于患者改善肌肉功能、改善EN吸收、提高摆脱肠外营养的机会、缓解胃肠道症状并提高生活质量。

关键词：肠系膜缺血短肠综合征康复研究血运重建

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Inside-out assembly of viral antigens for the enhanced vaccination

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3144-3157页

作者： Fengqiang Cao Sha Peng Yaling An Kun Xu Tianyi Zheng Lianpan Dai Kenji Ogino To Ngai yufei xia Guanghui Ma State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190PR China Graduate School of Bio-Applications and Systems Engineering Tokyo University of Agriculture and Technology2-24-16 NakachoKoganeiTokyo184-8588Japan Institute of Global Innovation Research Tokyo University of Agriculture and Technology2-24-16 NakachoKoganei-shiTokyo184-8588Japan CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101PR China Savaid Medical School University of Chinese Academy of SciencesBeijingPR China Key Laboratory of Tropical Translational Medicine of Ministry of Education School of Tropical Medicine and Laboratory MedicineThe First Affiliated HospitalHainan Medical UniversityHainan571199PR China Zhejiang University School of Medicine Hangzhou310058PR China Department of Chemistry The Chinese University of Hong KongShatinN.T.Hong Kong999077PR China University of Chinese Academy of Sciences Beijing100049PR China Innovation Academy for Green Manufacture Chinese Academy of Sciences Beijing100190PR China

Current attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens,but neglect that pathogens evolve to evade the immune system rather than to provoke *** the case of enveloped RNA viruses,it is the natural dissemination of nucleocapsid protein(NP,core antigen)and surface antigen that delays NP exposure to immune ***,we report a multi-layered aluminum hydroxide-stabilized emulsion(MASE)to dictate the delivery sequence of the *** this manner,the receptor-binding domain(RBD,surface antigen)of the spike protein was trapped inside the nanocavity,while NP was absorbed on the outside of the droplets,enabling the burst release of NP before *** with the natural packaging strategy,the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-potentiated environment in advance,which subsequently boosted CD40+DC activations and the engagement of the lymph *** both H1N1 influenza and SARS-CoV-2 vaccines,rMASE significantly increased antigen-specific antibody secretion,memory T cell engagement,and Th1-biased immune response,which diminished viral loads after lethal *** simply reversing the delivery sequence of the surface antigen and core antigen,the inside-out strategy may offer major implications for enhanced vaccinations against the enveloped RNA virus.

关键词： vaccination outside evolve

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