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SensFL:Privacy-Preserving Vertical Federated Learning with Sensitive Regularization

Computer Modeling in Engineering & Sciences 2025年第1期142卷 385-404页

作者： Chongzhen Zhang Zhichen Liu Xiangrui Xu fuqiang hu Jiao Dai Baigen Cai Wei Wang School of Automation and Intelligence Beijing Jiaotong UniversityBeijing100044China Shuohuang Railway Development Co. Ltd.National Energy GroupCangzhou062350China Beijing Key Laboratory of Security and Privacy in Intelligent Transportation School of Computer Science and TechnologyBeijing Jiaotong UniversityBeijing100044China

In the realm of Intelligent Railway Transportation Systems,effective multi-party collaboration is crucial due to concerns over privacy and data *** Federated Learning(VFL)has emerged as a promising approach to facilitate such collaboration,allowing diverse entities to collectively enhance machine learning models without the need to share sensitive training ***,existing works have highlighted VFL’s susceptibility to privacy inference attacks,where an honest but curious server could potentially reconstruct a client’s raw data from embeddings uploaded by the *** vulnerability poses a significant threat to VFL-based intelligent railway transportation *** this paper,we introduce SensFL,a novel privacy-enhancing method to against privacy inference attacks in ***,SensFL integrates regularization of the sensitivity of embeddings to the original data into the model training process,effectively limiting the information contained in shared *** reducing the sensitivity of embeddings to the original data,SensFL can effectively resist reverse privacy attacks and prevent the reconstruction of the original data from the *** experiments were conducted on four distinct datasets and three different models to demonstrate the efficacy of *** results show that SensFL can effectively mitigate privacy inference attacks while maintaining the accuracy of the primary learning *** results underscore SensFL’s potential to advance privacy protection technologies within VFL-based intelligent railway systems,addressing critical security concerns in collaborative learning environments.

关键词： Vertical federated learning privacy defenses

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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 ***, they are applied to precisely deliver drugs and promote the effect of cancer *** 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

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Self-oriented central-tumor delivery of legumain-cleavable vehicles governed by circulating monocyte/macrophage for precise tumor enrichment and immune activation

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Nano Research 2023年第4期16卷 5189-5205页

作者： Fangying Yu Xuwei Shang Yun Zhu Lijun Peng Simin Chen Tingting Meng Hong Yuan fuqiang hu College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China Department of Pharmacy Nanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Compressed blood and intratumoral lymphatic vessels induced by proliferated tumor cells and elevated interstitial fluid pressure produce regional hypoxic and necrotic region within tumors,which severely reduced the accessibility of immunogenic cell death(ICD)related drugs and immune-related ***,the strategy of self-oriented deep tumor delivery by circulating monocyte/macrophage was ***,CS-AI including an indoleamine 2,3-dioxygenase(IDO)inhibitor indoximod(IND)and hydrophilic chitosan(CSO)linked with alanine-alanine-asparagine(AAN)was prepared,which could be selectively cleaved by legumain overexpressed in macrophages and promote the collapse in ***,CS-AI was modified with mannose on the surface and further encapsulated the ICD inducer doxorubicin(DOX)to obtain M-CS-AI/*** intravenous injection,MCS-AI/DOX was specially recognized and internalized by circulating monocyte in *** formed drugs/monocyte tend to distribute in hypoxia/necrosis region guided by the homing signals released by *** monocytes then further differentiated into macrophages,up-regulating the expression of legumain and promoting the sensitive-release of chemo-drug DOX,IND,and the mannose-modified CSO(M-CSO).The released IND would specifically regulate immunosuppressive tumor microenvironment,and synergistically inhibit tumor growth with immune activation elements,ICD-induced DOX,and the favorable adjuvant *** summary,the self-oriented deep tumor delivery of legumain-cleavable nanovesicles through circulating monocyte makes it possible for reaching tumor regions inaccessible for nanoparticles and provides a novel insight for precise tumor enrichment and immune activation.

关键词： self-oriented circulating monocyte/macrophage hitchhike legumain-sensitive vehicles precise central-tumor enrichment immune activation

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Tumor and dendritic cell dual-targeting nanocarriers maximize the therapeutic potential of IDO1 inhibitor in vivo

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Nano Research 2022年第10期15卷 9204-9214页

作者： Tong Yu Xiangyu Jin Fangying Yu Xiqin Yang Yingping Zeng Tingting Meng Hong Yuan fuqiang hu Ocean College Zhejiang UniversityZhoushan 316021China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China

Researches on indoleamine-2,3-dioxygenase-1(IDO1),a neoplastic pathogenesis-related protein,have provided a new angle of view to regulate malignancy-related ***,the therapeutic efficacy of IDO1 inhibitors is subject to key limitations as both cancer and dendritic cells tend to be trapped in the IDO1-mediated immune dysfunction,which poses challenges to the inhibitory potency of drug regimens in multiple ***,we report on the fabrication technique of a biomimetic nanocarrier that is endowed with the whole array of cancer cell membrane proteins for encapsulating the most used IDO1 probe indoximod(IND).By fully utilizing the homologous adhesion proteins and antigenic motifs on cytomembrane,these nanoparticulate particles are capable of infiltrating tumors and actively accumulating in cancer and dendritic cells,as well as hitching a ride on dendritic cells to tumor-draining lymph ***,by increasing the distribution of drugs in both tumor cells and dendritic cells in tumor-draining lymph nodes,these formulations greatly enhance the efficacy of IND without the aid of chemotherapeutic drugs,achieving substantial control of tumor ***,this leverage of bionanotechnology maximizes the therapeutic potential of IND and can provide a theoretical reference for the clinical application of IDO1 inhibitors.

关键词： tumor cells dendritic cells dual-targeting nanocarriers indoleamine-2 3-dioxygenase-1(IDO1)

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Regulation of pathological blood-brain barrier for intracranial enhanced drug delivery and anti-glioblastoma therapeutics

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Oncology Research 2021年第5期29卷 351-363页

作者： KAI WANG FENGTIAN ZHANG CHANGLONG WEN ZHIhuA huANG ZHIHAO hu YUWEN ZHANG fuqiang hu LIJUAN WEN Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education Gannan Medical UniversityGanzhou341000China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou310058China Department of Orthopedics First Affiliated Hospital of Gannan Medical UniversityGanzhou341000China Medical College of Soochow University Suzhou215123China Department of Infectious Diseases Ganzhou People’s HospitalGanzhou341000China Ganzhou Key Laboratory of Neuroinflammation Research Gannan Medical UniversityGanzhou341000China

The blood-brain barrier(BBB)is an essential component in regulating and maintaining the homeostatic microenvironment of the central nervous system(CNS).During the occurrence and development of glioblastoma(GBM),BBB is pathologically destroyed with a marked increase in *** to the obstruction of the BBB,current strategies for GBM therapeutics still obtain a meager success rate and may lead to systemic ***,chemotherapy could promote pathological BBB functional restoration,which results in signiﬁcantly reduced intracerebral transport of therapeutic agents during multiple administrations of GBM and the eventual failure of GBM *** effective delivery of intracerebral drugs still faces severe ***,strategies that regulate the pathological BBB to enhance the transport of therapeutic agents across the barrier may provide new opportunities for the effective and safe treatment of *** article reviews the structure and function of BBB in physiological states,the mechanisms underlying BBB pathological fenestration during the development of GBM,and the therapeutic strategies of GBM based on BBB intervention and medicinal drugs transporting across the BBB.

关键词： Blood-brain barrier Physiological Pathological Glioblastoma Intervention

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Regulation of pathological BBB restoration via nanostructured ROS-responsive glycolipid-like copolymer entrapping siVEGF for glioblastoma targeted therapeutics

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Nano Research 2022年第2期15卷 1455-1465页

作者： Lijuan Wen Yu Peng Kai Wang Zhihua huang Shiying He Ruiwen Xiong Longping Wu Fengtian Zhang fuqiang hu National Engineering Research Center for Modernization of Tranditional Chinese Medicine-Hakka Medical Resources Branch College oj PharmacyGannan Medical UniversityGanzhou 341000China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Department of Orthopedics First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000China Department of Orthopedics Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education Gannan Medical UniversityGanzhou 341000China

Glioblastoma(GBM)is one of the malignant brain tumors with high mortality and no curative *** elevated vascular endothelial growth factor(VEGF)in GBM seriously disrupts the blood brain barrier(BBB)with an increased permeability,resulting in poor outcome and *** interference has shown strong potential to inhibit VEGF expression,thus it is necessary to development an effective and safe gene delivery system possessing the ability to cross the BBB and target GBM *** study aims to explore the anti-GBM effect of angiopep-2(Ap)peptide modified reactive oxygen species(ROS)cleavable thioketal(TK)linked glycolipid-like nanocarrier(CSTKSA)delivering anti-VEGF siRNA(R),termed as Ap-CSTKSA/R *** functionalized modification produced an enhanced cellular uptake and a stronger bio-distribution of Ap-CSTKSA/R complexes in U87 MG cells and brain tumor tissues,***-CSTKSA/R complexes exhibited great superiority in GBM growth inhibition and finally translated into the longest survival period mainly via receptor-mediated targeting delivery,VEGF gene silencing accompanied with remarkable angiogenesis inhibition,and suppressed expression of caveolin-1 which is involved in BBB functional regulation in the occurrence and treatment of *** study indicated that Ap functionalization on ROS-responsive glycolipid-like copolymer exhibits a promising and effective gene delivery platform for GBM targeted treatment.

关键词： glioblastoma ROS-responsive siRNA blood brain barrier copolymer

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Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 120-135页

作者： Xiaomei Wu Renxiang Yuan Yichong Xu Kai Wang Hong Yuan Tingting Meng fuqiang hu Department of Pharmacy Ruijin HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200000China College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China

The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.

关键词： Blood-brain barrier Lipid nanoparticles Brain delivery facilitation α-Symuclein Parkinson's disease

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SC79 promotes efficient entry of GDNF liposomes into brain parenchyma to repair dopamine neurons through reversible regulation of tight junction proteins

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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 *** 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 ***,a small molecular agonist SC79 was screened to open blood-brain barrier(BBB)and promote GDNF liposomes to get into ***79 reversibly reduces the expression of claudin-5,one of dominant tight junctions of *** study showed SC79 promoted liposomes to enter into brain parenchyma 2.43 times more than that of the *** 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

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ROS-responsive nanoparticles targeting inflamed colon for synergistic therapy of inflammatory bowel disease via barrier repair and anti-inflammation

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Nano Research 2024年第6期17卷 5409-5423页

作者： Ding Wang Qi Jiang Ruoyu Shen Lijun Peng Wentao Zhou Tingting Meng fuqiang hu Jianwei Wang Hong Yuan College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009China

The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological *** studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease(IBD).Oral administration is the most common route for intestinal *** this study,a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment,which can interrupt the pathological process of IBD,resulting in the significantly improved efficacy of existing *** on the specific pH values and high reactive oxygen species(ROS)levels in inflammatory sites of IBD,an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed,and confirmed in vitro and in *** anti-inflammatory drug dexamethasone acetate(Dex)and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions(TJs).The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with *** brief,a drug delivery system and a therapeutic strategy for IBD are successfully developed.

关键词： nanotechnology reactive oxygen species(ROS)-responsive targeted delivery inflammatory bowel disease(IBD) intestinal barrier combination treatment

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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 ***.7c and 7d in p.229 were *** upper left and bottom left pictures in Fig.7c were accidentally duplicated with the pictures at the sam... 详细信息

关键词： treatment picture

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