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Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

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Chinese Chemical Letters 2024年第6期35卷 385-391页

作者： An Lu Yuhao Guo Yi Yan Lin Zhai Xiangyu Wang Weiran Cao Zijie Li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan Liu huining he Zhiyu Wang Jian-Cheng Wang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Immuno-oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Department of Pharmacy Clinical Trial Research CenterChina-Japan Friendship HospitalBeijing 100029China Laboratory of innovative formulations and pharmaceutical excipients Ningbo Institute of Marine MedicinePeking UniversityNingbo 315832China

Immunosuppressive microenvironments present critical problems in clinical *** regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied *** this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for *** vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by ***,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint *** Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关键词： Chemo-immunotherapy Immune checkpoint inhibition Gene silencing Miriplatin Macrophage phagocytosis Nanotechnology

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Long acting carmustine loaded natural extracellular matrix hydrogel for inhibition of glioblastoma recurrence after tumor resection

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Frontiers of Chemical Science and Engineering 2022年第4期16卷 536-545页

作者： Sunhui Chen Qiujun Qiu Dongdong Wang Dejun She Bo Yin Meihong Chai huining he Dong Nyoung heo Jianxin Wang Department of Pharmaceutics School of PharmacyFudan University&Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 201203China Department of Radiology Huashan HospitalFudan UniversityShanghai 200040China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Dental Materials School of DentistryKyung Hee UniversitySeoul 02447Republic of Korea

Many scientific efforts have been made to penetrate the blood-brain barrier and target glioblastoma cells,but the outcomes have been *** attention should be given to local inhibition of recurrence after glioblastoma resection to meet real medical needs.A biodegradable wafer containing the chemotherapeutics carmustine(1,3-bis(2-chloroethyl)-1-nitrosourea,BCNU)was the only local drug delivery system approved for clinical glioblastoma treatment,but with a prolonged survival time of only two months and frequent side *** this study,to improve the sustained release and prolonged therapeutic effect of drugs for inhibiting tumor recurrence after tumor resection,both free BCNU and BCNU-poly(lactic-co-glycolic acid)(the ratio of lactic acid groups to glycolic acid groups is 75/25)nanoparticles were simultaneously loaded into natural extracellular matrix hydrogel from pigskin to prepare BCNU *** hydrogel was injected into the resection cavity of a glioblastoma tumor immediately after tumor removal in a fully characterized resection rat *** drugs were released instantly to kill the residual tumor cells,while drugs in nanoparticles were continuously released to achieve a continuous and effective inhibition of the residual tumor cells for 30 *** combined actions effectively restricted tumor growth in ***,this strategy of local drug implantation and delivery may provide a reliable method to inhibit the recurrence of glioblastoma after tumor resection in vivo.

关键词： BCNU glioblastoma recurrence tumor resection nanoparticles hydrogel

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Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles

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药学学报:英文版 2023年第9期13卷 3945-3955页

作者： Mei Lu Haonan Xing Wanxuan Shao Pengfei Wu Yuchuan Fan huining he Stefan Barth Aiping Zheng Xing-Jie Liang Yuanyu Huang Advanced Research Institute of Multidisciplinary Science School of Life ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Chinese Academy of Sciences(CAS)Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China South African Research Chair in Cancer Biotechnology Institute of Infectious Disease and Molecular Medicine(IDM)Department of Integrative Biomedical SciencesFaculty of Health SciencesUniversity of Cape TownCape Town 7925South Africa

Immunotherapy has revolutionized the landscape of cancer ***,single immunotherapy only works well in a small subset of *** immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic ***,the synergistic,additive or antagonistic antitumor effects of combined immunotherapies have been rarely ***,we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4(PAK4)silencing with immunogenic phototherapy in engineered extracellular vesicles(EVs)that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with si RNA against PAK4 and a photoactivatable *** engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy,thus contributing to effective antitumor effects in vitro and in ***,the antitumor synergism of the combined treatment was quantitatively determined by the Compu Syn *** combination index(CI)and isobologram results confirmed that there was an antitumor synergism for the combined ***,the dose reduction index(DRI)showed favorable dose reduction,revealing lower toxicity and higher biocompatibility of the engineered ***,the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs,which is promising for boosting the therapeutic outcome of cancer immunotherapy.

关键词： Antitumor synergism Combined cancer immunotherapy p21-activated kinase 4 RNA interference Immunogenic phototherapy Extracellular vesicles Immune infiltration CompuSyn

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Biosafety materials:Ushering in a new era of infectious disease diagnosis and treatment with the CRISPR/Cas system

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Biosafety and health 2022年第2期4卷 70-78页

作者： Yuquan Zhang Ziyue Li Julien Milon Essola Kun Ge Xuyan Dai huining he Haihua Xiao Yuhua Weng Yuanyu Huang School of Life Science School of Medical TechnologyAdvanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China Key Laboratory of Analytical Science and Technology of hebei Province College of Chemistry and Environmental ScienceKey Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of EducationHebei UniversityBaoding 071000China Hunan Agricultural University Changsha 410128China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Beijing National Laboratory for Molecular Science State Key Laboratory of Polymer Physical and ChemistryInstitute of ChemistryChinese Academy of ScienceBeijing 100190China School of Materials and the Environment Beijing Institute of TechnologyZhuhai 519085China

Despite multiple virus outbreaks over the past decade,including the devastating coronavirus disease 2019(COVID-19)pandemic,the lack of accurate and timely diagnosis and treatment technologies has wreaked havoc on global *** clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated proteins(Cas)system has the potential to address these critical needs for tackling infectious diseases to detect viral nucleic acids and inhibit viral *** review summarizes how the CRISPR/Cas system is being utilized for the treatment and diagnosis of infectious diseases with the help of biosafety materials and highlights the design principle and in vivo and in vitro efficacy of advanced biosafety materials used to deal with virus attacks.

关键词： Biosafety materials CRISPR/Cas SARS-CoV-2 Diagnosis Infectious disease

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An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5091-5106页

作者： Qiujun Qiu Sunhui Chen huining he Jixiang Chen Xinyi Ding Dongdong Wang Jiangang Yang Pengcheng Guo Yang Li Jisu Kim Jianyong Sheng Chao Gao Bo Yin Shihao Zheng Jianxin Wang Department of Pharmaceutics School of PharmacyFudan University&Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 201203China Department of Pharmacy Fujian Provincial Hospital&Provincial Clinical Medical College of Fujian Medical UniversityFuzhou 350001China Institute of Materia Medica Academy of Chinese and Western Integrative MedicineFudan UniversityShanghai 201203China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Radiology Huashan HospitalFudan UniversityShanghai 200040China Institute of Tropical Medicine Guangzhou University of Chinese MedicineGuangzhou 510006China Department of Neurosurgery Fujian Provincial Hospital&Provincial Clinical Medical College of Fujian Medical UniversityFuzhou 350001China

Despite exciting achievements with some malignancies,immunotherapy for hypoimmunogenic cancers,especially glioblastoma(GBM),remains a formidable clinical *** immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune ***,we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the"danger"signal of *** demonstrated the feasibility of this strategy in two scenarios of *** the first scenario,we showed that this simultaneous amplification system,in conjunction with local chemotherapy,enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model;thus,ultimately making a cold GBM hot and suppressing postoperative *** by excellent efficacy,we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM,a disease with limited clinical treatment *** general,this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractorymalignancies.

关键词： Immunotherapy Glioblastoma Antigen-capturing nanoparticles Recombinant chemokines Immune signal-amplifying

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Immobilization of penicillin G acylase onto amino-modified silica hydrogel

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Frontiers of Chemical Science and Engineering 2010年第1期4卷 87-90页

作者： Weibing DONG huining he Junbo GONG Victor CYANG Tianjin Key Laboratory for Modern Drug Delivery and High Efficiency School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China

Amino-modified silica hydrogel(N-MSHG)was prepared by a simple sol-gel processing via the cocondensation of commercial silica sol with *** G acylase(PGA),a model enzyme,was covalently immobilized onto the N-MSHG and then was used for the enzymatic synthesis of *** samples were characterized by Nitrogen sorption analysis,FT-IR and thermal gravimetric analysis(TGA).The results showed that the amino-modified gel was a mesoporous material with an average pore size of 12.64±0.17 *** immobilization process was efficient and the immobilized enzyme showed high catalytic *** yield of the synthesis of amoxicillin in aqueous media was 38%for 2.5 *** sol-gel preparation is simple and shows prominent potential value in industrial processing.

关键词： mesoporous materials covalent immobilization penicillin G acylase amino-modified silica gel

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Cellulose sub-nanometric ribbons:A new generation of nanocellulose and platform for biomaterials

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Journal of Bioresources and Bioproducts 2024年第1期9卷 1-2页

作者： Shaomin Kang Yang Zhao Junlong Song huining Xiao Jiangsu Co-Innovation Center for Efficient Processing and Utilization of Forest Resources and International Innovation Center for Forest Chemicals and Materials Nanjing Forestry UniversityNanjing 210037China Department of Chemical Engineering University of New BrunswickFredericton NB E3B 5A3Canada

With the tremendous progress of research in nanoscience,much attention has been paid to the bottom of the“nano world”:scales around one nanometer or even *** order to describe materials at this scale,a new concept c... 详细信息

关键词： biomaterials scales emerged

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Overcoming oral insulin delivery barriers： application of cell penetrating peptide and silica-based nanoporous composites

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Frontiers of Chemical Science and Engineering 2013年第1期7卷 9-19页

作者： huining he Junxiao YE Jianyong SheNG Jianxin WANG Yongzhuo HUANG Guanyi CheN Jingkang WANG Victor C YANG School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China Department of Pharmaceutics School of Pharmacy Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education & PLA Shanghai 201203 China Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China School of Environmental Science and Engineering State Key Laboratory of Engines Tianjin University Tianjin 300072 China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmacy Tianjin Medical University Tianjin 300070 China Department of Pharmaceutical Sciences College of Pharmacy University of Michigan Michigan 48109-1065 USA

Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations： the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin＇s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. Yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin＇s oral bioavailability. In this review of our group＇s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide （CPP） to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPPinsulin conjugates could facilitate cellular uptake of insulin while keeping insulin＇s biologic functions intact. It was also confirmed that low molecular weight protamine （LMWP） behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan （25wt-%） and silica （75 wt-%） exhibited the greatest mucoadhesion at gastric pH. Furthermore, drugrelease from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

关键词： insulin cell penetrating peptide mucoadhesive composites oral delivery

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A creep model for ultra-deep salt rock considering thermal-mechanical damage under triaxial stress conditions

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第2期16卷 588-596页

作者： Chao Liang Jianfeng Liu Jianxiong Yang huining Xu Zhaowei Chen Lina Ran College of Water Resource and Hydropower Sichuan UniversityChengdu610065China CNPC Key Laboratory of Oil and Gas Underground Storage Engineering Langfang065007China CNPC Engineering Technology R&D Company Limited Beijing102206China

To investigate the specific creep behavior of ultra-deep buried salt during oil and gas exploitation,a set of triaxial creep experiments was conducted at elevated temperatures with constant axial pressure and unloading confining pressure *** results show that the salt sample deforms more significantly with the increase of applied temperature and deviatoric *** accelerated creep phase is not occurring until the applied temperature reaches 130℃,and higher temperature is beneficial to the occurrence of accelerated *** describe the specific creep behavior,a novel three-dimensional(3D)creep constitutive model is developed that incorporates the thermal and mechanical variables into mechanical ***,the standard particle swarm optimization(SPSO)method is adopted to fit the experimental data,and the sensibility of key model parameters is analyzed to further illustrate the model *** a result,the model can accurately predict the creep behavior of salt under the coupled thermo-mechanical effect in deep-buried *** on the research results,the creep mechanical behavior of wellbore shrinkage is predicted in deep drilling projects crossing salt layer,which has practical implications for deep rock mechanics problems.

关键词： Creep experiments Creep model Thermal and mechanical damage Fractional derivative

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Ultrasound-mediated targeted microbubbles： a new vehicle for cancer therapy

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Frontiers of Chemical Science and Engineering 2013年第1期7卷 20-28页

作者： Junxiao YE huining he Junbo GONG Weibing DONG Yongzhuo HUANG Jianxin WANG Guanyi CheN Victor C YANG School of Chemical Engineering and Technology Tianjin University Tianjin 300072 China Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Department of Pharmaceutics School of Pharmacy Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education & PLA Shanghai 201203 China School of Environmental Science and Engineering State Key Laboratory of Engines Tianjin University Tianjin 300072 China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of Pharmacy Tianjin Medical University Tianjin 300070 China Department of Pharmaceutical Sciences College of Pharmacy University of Michigan Ann Arbor MI 48109-1065 USA

With the hope of overcoming the serious side effects, great endeavor has been made in tumor-targeted chemotherapy, and various drug delivery modalities and drug carriers have been made to decrease systemic toxicity caused by chemotherapeutic agents. Scientists from home and abroad focus on the research of targeted microbubbles contrast agent, and the use of the targeted ultrasound microbubble contrast agent can carry gene drugs and so on to the target tissue, as well as mediated tumor cell apoptosis and tumor microvascular thrombosis block, etc., thus plays the role of targeted therapy. Recent studies have elucidated the mechanisms of drug release and absorption, however, much work remains to be done in order to develop a successful and optimal system. In this review, we summarized the continuing efforts in under-standing the usage of the ultrasound triggered target microbubbles in cancer therapy, from release mechanism to preparation methods. The latest applications of ultra-sound-triggered targeted microbubbles in cancer therapy, especially in gene therapy and antiangiogenic cancer therapy were discussed. Moreover, we concluded that as a new technology, ultrasound-triggered targeted microbubbles used as drug carriers and imaging agents are still energetic and are very likely to be translated into clinic in the near future.

关键词： ultrasound-mediated targeted microbubbles cancer

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