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O_(2)-generating multifunctional polymeric micelles for highly efficient and selective photodynamic-photothermal therapy in melanoma

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Chinese Chemical Letters 2024年第7期35卷 394-399页

作者： Yu Qin Mingyang huang chenlu huang Hannah LPerry Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China Molecular Sciences Research Hub Department of ChemistryWhite City CampusImperial College LondonLondon W120BZUnited Kingdom

Photothermal therapy(PTT)and photodynamic therapy(PDT)have received tremendous attention owing to their great potential for tumor ***,two main issues hamper the antitumor performance of PDT:overexpression of glutathione(GSH)in tumors,which consumes PDT-induced reactive oxygen species(ROS),and hypoxia within the tumor *** drawbacks of PTT include uneven temperature distribution and the upregulation of the heat-shock proteins in tumors,both of which result in ineffective *** address these issues,a MnO_(2)doped nano-delivery system(HTIM-PMs)was synthesized by one-step self-assembly of disulfide bond bridged copolymers for indocyanine green(ICG)and MnO_(2)*** surface of polymeric micelles was layered with hyaluronan(HA)and transactivator(TAT)peptides to improve active targeting and increase cell *** internalization,HTIM-PMs showed responsiveness to the tumor microenvironment(acid pH,high glutathione,high H_(2)O_(2)).Breaking the disulfide bond reduced the intratumoral GSH level and simultaneously released the MnO_(2)and *** released MnO_(2)further reduced the GSH level and promoted O_(2)generation,thus enhancing the PDT *** PTT-mediated hyperthermia accelerated blood flow,which is beneficial for O_(2)distribution,and promotes ROS *** PTT-mediated adjuvant effects further overcame the limitations of PDT and the robust PDT effect in turn compensated for the deficiency of *** promising platform exhibited a significant improvement in the PTT-PDT cancer treatment strategy compared to previously reported nanostructures.

关键词： Photodynamic therapy Photothermal therapy Oxygen generating One-step self-assembly Stimuli-responsive nanoparticles

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Gas-generating polymersomes-based amplified photoimmunotherapy for abscopal effect and tumor metastasis inhibition

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Chinese Chemical Letters 2024年第6期35卷 456-461页

作者： chenlu huang Xinyu Yang Qingyu Yu Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Due to the heterogeneity of tumors,single phototherapy cannot completely ablate tumors and inhibit tumor *** overcome these,we formulated targeted and multifunctional polymersomes ABC@ICGIMQ-LHRH(AIRL)that encapsulated Toll-like receptor(TLR)7/8 agonist imiquimod(IMQ)and photosensitizer indocyanine green(ICG)in the hydrophobic layer as well as bubble-generator NH_(4)HCO_(3) in the hydrophilic cavity to inhibit the growth of primary and distant tumors,and prevent tumor metastasis through synergistic *** AIRL polymersomes exhibited uniform and stable size,and high drug encapsulation efficiency,acid/reduction/laser responsiveness,excellent photothermal conversion efficiency,effective reactive oxygen species generation,high tumor *** could be effectively internalized by dendritic cells(DCs),achieve lysosome escape and enhance DCs *** synergistic photoimmunotherapy via AIRL polymersomes remarkably promoted the differentiation and activation of T cells,elevated strong systemic immune response to eradicate primary tumors and inhibit the growth of distant ***,the endurable immunological memory prevented tumor metastasis,which provided a promising nanoplatform for the combination therapy of cancer.

关键词： Polymersomes Phototherapy Immunotherapy TLR 7/8 agonist Gas-generating

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Spatio-temporal delivery of both intra-and extracellular toll-like receptor agonists for enhancing antigen-specific immune responses

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4486-4500页

作者： Nannan Wang Yueyue Zuo Shengjie Wu chenlu huang Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

For cancer immunotherapy,triggering toll-like receptors(TLRs)in dendritic cells(DCs)can potentiate antigen-based immune ***,to generate robust and long-lived immune responses,a well-designed nanovaccine should consider different locations of TLRs on DCs and co-deliver both antigens and TLR agonist combinations to synergistically induce optimal antitumor ***,we fabricated lipid-polymer hybrid nanoparticles(LPNPs)to spatio-temporally deliver model antigen ovalbumin(OVA)on the surface of the lipid layer,TLR4 agonist monophosphoryl lipid A(MPLA)within the lipid layer,and TLR7 agonist imiquimod(IMQ)in the polymer core to synergistically activate DCs by both extra-and intra-cellular TLRs for enhancing adaptive immune ***-based nanovaccines exhibited a narrow size distribution at the mean diameter of 133.23 nm and zeta potential of−2.36 mV,showed a high OVA loading(around 70.83μg/mg)and IMQ encapsulation efficiency(88.04%).Our data revealed that LPNPs-based nanovaccines showed great biocompatibility to immune cells and an excellent ability to enhance antigen internalization,thereby promoting DCs maturation and cytokines *** to Free OVA,OVA-LPNPs promoted antigen uptake,lysosome escape,depot effect and migration to secondary lymphatic *** vivo immunization showed that IMQ-MPLA-OVA-LPNPs with dual agonists induced more powerful cellular and humoral immune ***,prophylactic vaccination by IMQ-MPLA-OVA-LPNPs effectively suppressed tumor growth and increased survival ***,the nanovaccines we fabricated can effectively co-deliver antigens and different TLR agonists and realize coordinated stimulation of DCs in a spatio-temporal manner for enhanced immune responses,which provides a promising strategy for cancer immunotherapy.

关键词： Lipid-polymer hybrid nanoparticles TLR agonist combinations Ovalbumin Monophosphoryl lipid AImiquimod Nanovaccine Spatio-temporal manner Cancer immunotherapy

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DRG支付方式下脑出血患者住院费用影响因素分析

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中国卫生标准管理 2024年第6期15卷 56-60页

作者：郑舒妮黄晨璐潘志刚福建医科大学附属第二医院办公室福建泉州362000 福建医科大学附属协和医院运营管理处福建福州350000 福建医科大学附属第二医院神经外科福建泉州362000

目的对比福建医科大学附属第二医院脑出血患者在实行疾病诊断相关分组(diagnosis related groups,DRG)支付方式前后的住院费用,并分析其影响因素,为有效调整区域化DRG费用标准提供参考依据。方法本研究以福建医科大学附属第二医院2021年... 详细信息

目的对比福建医科大学附属第二医院脑出血患者在实行疾病诊断相关分组(diagnosis related groups,DRG)支付方式前后的住院费用,并分析其影响因素,为有效调整区域化DRG费用标准提供参考依据。方法本研究以福建医科大学附属第二医院2021年9月—2023年6月病案首页诊断编码(疾病分类代码国临版2.0)为I60~I62的病例为研究对象,采用Kendall相关性分析进行单因素分析,将差异有统计学意义的变量纳入多元线性回归模型进行多因素分析。结果实行DRG支付费改革后,脑出血住院患者平均住院费用与自付金额分别下降26.17%和45.55%,控费效果较好;DRG支付方式下对住院费用影响最大的前4位因素是住院天数、是否手术、出院时已治愈以及住院时病重状态;DRG支付方式下,脑出血相关DRG分组呈盈利状态。结论DRG支付方式有效实现控费目标,改革成效明显;医疗机构应注意缩短住院天数,合理提高体现医疗价值的治疗费用占比,减少不必要的医药、耗材、检查等支出;医保部门应考虑将住院天数纳入DRG分组标准,综合考虑医疗服务质量、医保支付能力、患者个人经济负担,动态调整DRG分组支付标准。

关键词： DRG 脑出血费用分析支付方式住院患者 Kendall相关性分析

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Programmed polymersomes with spatio-temporal delivery of antigen and dual-adjuvants for efficient dendritic cells-based cancer immunotherapy

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Chinese Chemical Letters 2022年第9期33卷 4179-4184页

作者： Hanyong Wang Xinyu Yang Chunyan Hu chenlu huang Hai Wang Dunwan Zhu Linhua Zhang Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China

Since antigen and adjuvant are rapid clearance in vivo,insufficient delivery to induce dendritic cells(DCs)maturation and cross-presentation,as well as limited migration efficiency of DCs to secondary lymph organs,greatly hinders the development of DCs-based ***,PCL-PEG-PCL polymersomes(PCEP-PS)as antigen and adjuvants delivery nanoplatforms(IMO-PS)were well-designed,which can electrostatically adsorb OVA antigen on the surface via DOTAP lipid and effectively encapsulate OVA antigen into the inner hydrophilic cavity to achieve both initial antigen exposure as well as slow and sustained antigen release,incorporate MPLA within the lipid layer to ligate with extracellular TLR4 of DCs as well as encapsulate IMQ in the hydrophobic membrane to ligate with intracellular TLR7/8 of DCs for activating synergistic immune responses via different signaling *** IMO-PS significantly improved antigen uptake,promoted DCs maturation and cytokines *** treated with IMO-PS could enhance migration into draining lymphoid nodes,and eventually induced antigen-specific CD8+and CD4+T cell responses and OVA-specific cytotoxic T lymphocyte(CTL)*** vaccination of EG7-OVA tumor-bearing mice by IMO-PS+DCs significantly extended tumor-free time,effectively suppressed tumor growth,and greatly extended median survival *** strategy may provide an effective nanoplatform for co-delivery antigen and dual-adjuvants in a spatio-temporally programmed manner for DC-based cancer immunotherapy.

关键词： DCs vaccine Immunotherapy Imiquimod MPLA DOTAP OVA

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Folate-targeted co-delivery polymersomes for efficient photo-chemo-antiangiogenic therapy against breast cancer and in vivo evaluation via OCTA/NIRF dual-modal imaging

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Chinese Chemical Letters 2022年第12期33卷 5035-5041页

作者： Hongjun Wu chenlu huang Liwei Wang Qinghua Li Yuejie Li Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Intelligent nanoplatform that combines multimodal imaging and therapeutic effects holds great promise for precise and efficient cancer ***,folate-targeted polymersomes with stimuli-responsiveness were fabricated and evaluated by near-infrared fluorescence(NIRF)and optical coherence tomography angiography(OCTA)dual-imaging for photo-chemo-antiangiogenic therapy against *** folate-targeted polymersomes(FA-MIT-SIPS)not only integrated ammonium bicarbonate(ABC)and mitoxantrone(MIT)into their hydrophilic cavity but also encapsulated indocyanine green(ICG)and sorafenib(SOR)within their hydrophobic *** imaging demonstrated that FA-MIT-SIPS effectively accumulated and retained in the *** 808 nm laser irradiation,the ICG produced hyperthermia and reactive oxygen species(ROS)for efficient photothermal and photodynamic *** addition,the decomposition of ABC in responsive to acidic tumor environment and ICG-induced hyperthermia accelerated drug *** released MIT accumulated in nucleus to inhibit DNA synthesis,while the released SOR destructed tumor ***,OCTA imaging was applied to observe the tumor blood flow upon the combination therapy,demonstrating that FA-MIT-SIPS obviously decreased the vessels area ***,the synergistic photo-chemo-antiangiogenic therapy of FA-MIT-SIPS achieved excellent antitumor effect with 40%of the 4T1 tumor-bearing mice being completely cured without *** multifunctional polymersomes provide a promising dual-modal imaging-evaluated synergistic strategy for tumor therapy.

关键词： Polymersomes Optical coherence tomography angiography(OCTA) Near infrared fluorescence(NIRF)imaging Photo-chemo-antiangiogenic therapy Intelligent nanoplatform

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LHRH/TAT dual peptides-conjugated polymeric vesicles for PTT enhanced chemotherapy to overcome hepatocellular carcinoma

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Chinese Chemical Letters 2020年第12期31卷 3121-3126页

作者： Yu Qin Qing Guo Shengjie Wu chenlu huang Zhiming Zhang Li Zhang Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Combination therapy such as photothermal therapy(PTT)enhanced chemotherapy is regarded as a promising strategy for cancer ***,we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer *** avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance,the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics:doxorubicin(DOX)and paclitaxel(PTX).Besides,indocyanine green(ICG)was encapsulated,and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric *** results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content,trigger drug release in responsive to the reductive environment,realize high cellular uptake via dual peptides and laser irradiation,and achieve higher cytotoxicity via chemo-photothermal combination ***,the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.

关键词： Redox-responsive Polymeric vesicles Chemotherapy Photothermal therapy Combination therapy

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Reconfigurable intelligent surfaces for smart wireless environments: channel estimation, system design and applications in 6G networks

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Science China(Information Sciences) 2021年第10期64卷 52-72页

作者： Ying-Chang LIANG Jie CHEN Ruizhe LONG Zhen-Qing HE Xianqi LIN chenlu huang Shilin LIU Xuemin (Sherman) SHEN Marco DI RENZO Center for Intelligent Networking and Communications University of Electronic Science and Technology of China School of Electronic Science and Engineering University of Electronic Science and Technology of China Department of Electrical and Computer Engineering University of Waterloo Université Paris-Saclay CNRS CentraleSupélec Laboratoire des Signaux et Systèmes

Reconfigurable intelligent surface(RIS), one of the key enablers for the sixth-generation(6G)mobile communication networks, is considered by designers to smartly reconfigure the wireless propagation environment in a controllable and programmable manner. Specifically, an RIS consists of a large number of low-cost and passive reflective elements(REs) without radio frequency chains. The system gain of RIS wireless systems can be achieved by adjusting the phase shifts and amplitudes of the REs so that the desired signals can be added constructively at the receiver. However, an RIS typically has limited signal processing capability and cannot perform active transmitting/receiving in general, which leads to new challenges in the physical layer design of RIS wireless systems. In this paper, we provide an overview of the RIS-aided wireless systems, including the reflection principle, channel estimation, and system design. In particular,two types of emerging RIS systems are considered: RIS-aided wireless communications(RAWC) and RISbased information transmission(RBIT), where the RIS plays the role of the reflector and the transmitter,respectively. We also envision the potential applications of RIS in 6G networks.

关键词： reconfigurable intelligent surface channel estimation RIS-aided wireless communications RIS-based information transmission 6G

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A New Algorithm Based on Differential Transform Method for Solving Partial Differential Equation System with Initial and Boundary Conditions

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Advances in Pure Mathematics 2020年第5期10卷 337-349页

作者： chenlu huang Jiwei Li Fali Lin School of Architecture and Civil Engineering Taizhou University Taizhou China

In this paper, a new Fourier-differential transform method (FDTM) based on differential transformation method (DTM) is proposed. The method can effectively and quickly solve linear and nonlinear partial differential equations with initial boundary value (IBVP). According to boundary condition, the initial condition is expanded into a Fourier series. After that, the IBVP is transformed to an iterative relation in K-domain. The series solution or exact solution can be obtained. The rationality and practicability of the algorithm FDTM are verified by comparisons of the results obtained by FDTM and the existing analytical solutions.

关键词： Differential Transform Method Initial Boundary Value Problem Fourier-Differential Transform Method Fourier Series Typical Zero Boundary

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pH-sensitive and bubble-generating mesoporous silica-based nanoparticles for enhanced tumor combination therapy

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Acta Pharmaceutica Sinica B 2021年第2期11卷 520-533页

作者： Zhiming Zhangy chenlu huangy Li Zhang Qing Guo Yu Qin Fan Fan Boxuan Li Bao Xiao Dunwan Zhu Linhua Zhang Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Chemotherapy has been a major option in clinic treatment of malignant ***,single chemotherapy faces some drawbacks,such as multidrug resistance,severe side effects,which hinder its clinic application in tumor *** nanoparticles loading with chemotherapeutic agent and photosensitizer could be a promising way to efficiently conduct tumor combination *** the current study,a novel pH-sensitive and bubble-generating mesoporous silica-based drug delivery system(denoted as M(a)D@PI-PEG-RGD)was *** bicarbonate(NH4 HCO3;abc)and chemotherapeutic agent doxorubicin(DOX)were loaded into the pores of mesoporous *** green(ICG)as a photothermal and photodynamic agent was loaded onto the polydopamine(PDA)layer *** synthesized nanoparticles displayed a narrow polydispersity(PDI)and small particle size as characterized through dynamic light scattering-autosizer *** nanoparticles also showed high targeting efficacy through RGD modification as indicated by cellular uptake and animal *** release analysis confirmed that the nanoparticles were pH-dependent and that NH4 HCO3 accelerated drug *** the same time,the nanoparticles had obvious photothermal and photodynamic effects performed by ICG which restrained tumor growth *** summary,the multifunctional nanoparticles presented a promising system for combination therapy.

关键词： Mesoporous silica pH-sensitive Bubble-generating Targeting modification Combination therapy

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