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Bacterial and cancerous cell membrane fused liposome coordinates with PD-L1 inhibitor for cancer immunotherapy

Nano Research 2024年第9期17卷 8389-8401页

作者： Xianjin Luo Chenglong Li Zhaofei Guo Hairui Wang Penghui he Yuanhao Zhao Yi Lin chunting he Yingying Hou Yongshun Zhang Guangsheng Du Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610064China Pharmaceutical Biotechnology Department of PharmacyLMU MunichButenandt Strasse 5-13Munich 81377Germany Department of Biomedical Engineering College of Future TechnologyPeking UniversityBeijing 100871China

Although tumor cell membranes with broad-spectrum antigens have been explored for cancer vaccines for decades,their relatively poor capacity to stimulate immune responses,especially cellular immune responses,has limited their ***,we presented a novel bacterial and cancerous cell membrane fusogenic liposome for co-delivering cell membrane-derived antigens and ***,a programmed death-ligand 1(PD-L1)inhibitor,JQ-1,was incorporated into the formulation to tackle the up-regulated PD-L1 expression of antigen-presenting cells(APCs)upon vaccination,thereby augmenting its anti-tumor *** fusogenic liposomes demonstrated significantly improved cellular uptake by APCs and effectively suppressed PD-L1 expression in bone marrow-derived dendritic cells(BMDCs)in *** subcutaneous vaccination,the nano-vaccines efficiently drained to the tumor-draining lymph nodes(TDLNs),and significantly inhibited PD-L1 expression of both dendritic cells(DCs)and macrophages within the TDLNs and *** a result,the liposomal vaccine induced robust innate and cellular immune responses and inhibited tumor growth in a colorectal carcinoma-burden mouse *** summary,the fabricated cell membrane-based fusogenic liposomes offer a safe,effective,and easily applicable strategy for tumor immunotherapy and hold potential for personalized cancer immunotherapy.

关键词： fusogenic liposome tumor cell membrane adjuvant programmed death-ligand 1(PD-L1)inhibitor tumor draining lymph nodes

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Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

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Acta Pharmaceutica Sinica B 2024年第1期14卷 350-364页

作者： Yongshun Zhang Lan Yang Yangsen Ou Rui Hu Guangsheng Du Shuang Luo Fuhua Wu Hairui Wang Zhiqiang Xie Yu Zhang chunting he Cheng Ma Tao Gong Ling Zhang Zhirong Zhang Xun Sun Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)***,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB ***,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor *** demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell ***,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in *** order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor *** anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

关键词： Triple therapy Adeno-associated virus PTEN PPSG@anti-PD-1 CpG Immunogenic cell death Antitumor immune response Immune memory

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Highly pathogenic coronaviruses: thrusting vaccine development in the spotlight

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Acta Pharmaceutica Sinica B 2020年第7期10卷 1175-1191页

作者： chunting he Ming Qin Xun Sun Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China

Coronaviruses(CoVs)are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Severe Acute Respiratory Syndrome(SARS)and Middle East Respiratory Syndrome(MERS).Severe Acute Respiratory Syndrome coronavirus 2(SARS-CoV-2)disease(COVID-19)has caused major public health *** have been more than 4,400,000 reported cases of COVID-2019 and more than 300,000 reported deaths to date(16/05/2020).SARS-CoV,MERSCoV and SARS-CoV-2 have attracted widespread global attention due to their high infectivity and *** date,there is no specific treatment proven effective against these viral infectious *** is considered one of the most effective strategies to prevent viral ***,the development of effective vaccines against highly pathogenic coronaviruses is *** this review,we will briefly describe coronavirus vaccine design targets,summarize recent advances in the development of coronavirus vaccines,and highlight current adjuvants for improving the efficacy of coronavirus vaccines.

关键词： Coronaviruses SARS-CoV MERS-CoV SARS-CoV-2 Vaccine Adjuvant

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Solid-state molecular dynamics of a torsion-variable ammonium embedded in a deformable supramolecular framework

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Chinese Journal of Structural Chemistry 2023年第2期42卷 23-28页

作者： Hui Xiao Liwen Ding Jingyan Liu Zhihui Jia Liming Cao Ziyi Du chunting he College of Chemistry and Chemical Engineering Jiangxi Normal UniversityNanchang 330022China College of Chemistry Fuzhou UniversityFuzhou350108China

Accompanied by solid-state structural phase transitions,the switchable molecular dynamics(MD)and order-disorder transformation of(i-PrNHMe2)^(+)cation embedded in a deformable{[Ni(NCS)_(6)]^(4-)}_(∞)supramolecular framework are in-depth investigated by variable-temperature tests of single-crystal X-ray diffraction,dielectric measurement,and MD ***,it is found that the confined swinging or flipping of the(i-PrNHMe_(2))^(+)cation as a whole is assisted by a synergistic change of its torsion *** research provides a helpful insight into the solid-state MD of moderate-sized quasi-spherical molecules/ions that feature a flexible inner core.

关键词： Solid-state molecular dynamics Supramolecular framework Phase transition Dielectric

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An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3518-3534页

作者： Yunting Zhang Min Jiangy Guangsheng Du Xiaofang Zhong chunting he Ming Qin Yingying Hou Rong Liu Xun Sun Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

The rise of nanotechnology has opened new horizons for cancer ***,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictable metabolism,and potential systemic toxicity,which bring obstacles for their clinical ***,we developed an antigen self-assembled nanovaccine,which was resulted from a simple acryloyl modification of the antigen to induce ***,a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid(Zol)were integrated or absorbed onto the nanoparticles(denoted as MEAO-Z)to intensify the immune *** synthesized nano vaccine with a diameter of around 70 nm showed successful lymph node transportation,high dendritic cell internalization,promoted costimulatory molecule expression,and preferable antigen *** virtue of the above superiorities,MEAO-Z induced remarkably higher titers of serum antibody,stronger cytotoxic T lymphocyte immune responses and IFN-γsecretion than free antigen and *** vivo,MEAO-Z significantly suppressed EG7-OVA tumor groth and prolonged the survival time of tumor-bearing *** results indicated the translation promise of our self-assembled nano vaccine for immune potentiation and cancer immunotherapy.

关键词： Subunit antigen Self-assembled nanovaccine Dendritic cell Mannose receptor Zoledronic acid Antigen cross-presentation Cellular immunity Cancer immunotherapy

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Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2219-2233页

作者： Fuhua Wu Shuang Luo Yongshun Zhang Yangsen Ou Hairui Wang Zhaofei Guo chunting he Shuting Bai Penghui he Min Jiang Xiaoyan Chen Guangsheng Du Xun Sun Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines,the epidemic prevention and control are still ***,we employ a capsid and antigen structure engineering(CASE)strategy to manufacture an adenoassociated viral serotype 6-based vaccine(S663V-RBD),which expresses trimeric receptor binding domain(RBD)of spike protein fused with a biological adjuvant ***,the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 *** to the licensed BBIBP-CorV(Sinopharm,China),a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type,C.37(Lambda)and B.1.617.2(Delta).More interestingly,the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the *** its effectiveness,the CASE-based S663VRBD may provide a new solution for the current and next pandemic.

关键词： AAV vectors Capsid engineering Vaccine Antigen structure design SARS-CoV-2

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Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2934-2949页

作者： Jiao Xue Yining Zhu Shuting Bai chunting he Guangsheng Du Yuandong Zhang Yao Zhong Wenfei Chen Hairui Wang Xun Sun Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Photothermal therapy has been intensively investigated for treating cancer in recent ***,the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and *** address this challenge,immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor ***,we engineered silica-based core-shell nanoparticles(JQ-1@PSNs-R),in which silica cores were coated with the photothermal agent polydopamine,and a bromodomain-containing protein 4(BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photo thermal and immune therapy for tumor ***,to improve the therapeutic effect,we increased the surface roughness of the nanoparticles by hydrofluoric acid(HF) etching during the fabrication process,and found that the internalization of JQ-1@PSNs-R was significantly improved,leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of *** the animal studies,the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy,successfully activated tumor-specific immune responses against residual tumor cells,and further prevented tumor metastasis and *** results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.

关键词： Photothermal therapy Immunotherapy Rough surface Polydopamine-coated silica nanoparticles JQ-1 Melanoma

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Event-triggered adaptive output feedback control for hyperbolic PDEs: swapping-based design

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Science China(Information Sciences) 2024年第5期67卷 327-328页

作者： chunting JI Zhengqiang ZHANG Xue-Jun XIE School of Engineering Qufu Normal University Institute of Automation Qufu Normal University

Partial differential equations(PDEs) characterize transport phenomena and fluid flow, and common cases include heat exchangers and road traffic [1]. Recently, scholars have become enthusiastic about event-triggered control(ETC) of hyperbolic PDEs, primarily because it can help conserve computing and communication resources. For example,Ref. [2] presented an output feedback ETC scheme for 2 × 2hyperbolic PDEs.

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Smart beam via electrically addressing the dye-doped and polymer-stabilized cholesteric liquid crystals

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Chinese Optics Letters 2024年第5期22卷 111-116页

作者：彭程徐春庭胡伟 College of Engineering and Applied Sciences Nanjing UniversityNanjing 210023China

Smart beams play a vital role in modern intelligent vehicles and have recently attracted significant attention.A spatial light modulator with high optical efficiency,low cost,and compact size is crucial for designing smart ***,we mix cholesteric liquid crystals with dichroic black dye and a *** UV polymerization,the sample exhibits a low driving voltage of 26 V,a high transmittance of over 70%,and an On-off ratio over 280,thanks to the joint contribution of both the absorption and the scattering effect.A smart beam device is demonstrated by electrically addressing the dye-doped and polymer-stabilized cholesteric liquid crystal with pixelated *** patterns with arbitrary designs are projected *** switching time reaches several tens of *** strategy brings new designs to intelligent vehicles and may also inspire applications in public information displays,advertising,and even AR/VR displays.

关键词： cholesteric liquid crystal spatial light modulation smart beam dye guest-host effect

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从联想的发展看组织结构的变革与设计

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管理观察 2014年第35期 51-53页

作者：何潇何春婷重庆商务职业学院重庆北恒投资发展有限公司重庆404100

本文以联想为例分别讨论了直线制、事业部制和矩阵制三种企业组织结构的基本形式。意在使相关企业能够在适合自身发展的阶段制定适合自己的组织结构,优化企业管理。

关键词：联想组织结构组织设计

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