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Application of Nano-Delivery systems in Lymph Nodes for tumor Immunotherapy

Nano-Micro Letters 2023年第9期15卷 275-309页

作者： Yiming Xia Shunli Fu Qingping Ma Yongjun Liu Na Zhang Department of Pharmaceutics Key Laboratory of Chemical Biology(Ministry of Education)NMPA Key Laboratory for Technology Research and Evaluation of Drug ProductsSchool of Pharmaceutical SciencesCheeloo College of MedicineShandong University44 Wenhua Xi RoadJinan 250012ShandongPeople’s Republic of China

Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LNs),*** unique structure of LNs provides the microenvironment suitable for the survival,activation,and proliferation of multiple types of immune *** play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor *** taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes ***,the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy ***,LNs have become a key target for tumor ***,the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells,which leads to unsatisfactory anti-tumor *** efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune ***-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues,exhibiting powerful and promising prospects for achieving effective delivery to ***,the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed ***,developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.

关键词： Cancer therapy Immunotherapy Lymph nodes Nano-delivery systems

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Detection and surveillance of circulating tumor cells in osteosarcoma for predicting therapy response and prognosis

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Cancer Biology & Medicine 2022年第9期19卷 1397-1409页

作者： Haoran Mu Dongqing Zuo Jie Chen Zhigang Liu Zhuo Wang Liu Yang Qihui Shi Yingqi Hua Shanghai Bone tumor Institute and Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Key laboratory of systems Biomedicine(Ministry of Education) Shanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghai 200240China Shanghai Key laboratory of Medical Epigenetics and the International Co-laboratory of Medical Epigenetics and Metabolism(MOST) Institutes of Biomedical SciencesFudan UniversityShanghai 200032China Key laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer(SMHC)and Institute of Fudan-Minhang Academic Health System Minhang HospitalFudan UniversityShanghai 201199China Shanghai Engineering Research Center of Biomedical Analysis Reagents Shanghai 201203China

Objective:Osteosarcoma(OS)is an aggressive,highly metastatic,relatively drug-resistant bone tumor with poor long-term survival *** presence and persistence of circulating tumor cells(CTCs)in the peripheral blood are believed to be associated with treatment inefficiency and distant metastases.A blood-based CTC test is thus greatly needed for monitoring disease progression and predicting clinical ***,traditional methods cannot detect CTCs from tumors of mesenchymal origin such as OS,and research on CTC detection in mesenchymal tumors has been hindered for ***:In this study,we developed a CTC test based on hexokinase 2,a metabolic function-associated marker,for the detection and surveillance of OS CTCs,and subsequently explored its clinical *** patients with OS were enrolled as the training cohort for serial CTC *** CTC counting,in combination with therapy evaluation and post-treatment follow-up,was used to establish a model for predicting post-chemotherapy evaluation and disease-free survival,and the model was further validated with a cohort of 8 patients with ***:Two dynamic CTC number patterns were identified,and the resulting predictive model exhibited 92%consistency with the clinical *** model suggested that a single CTC test has similar predictive power to serial CTC *** the validation cohort,the single CTC test exhibited 100%and 87.5%consistency with therapy response and disease-free survival,***:Our non-invasive test for detection and surveillance of CTCs enables accurate prediction of therapy efficiency and prognosis,and may be clinically valuable for avoiding inefficient therapy and prolonging survival.

关键词： Circulating tumor cells osteosarcoma hexokinase 2 single-cell sequencing mesenchymal tumor

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The theory of tumor ecosystem

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Cancer Communications 2022年第7期42卷 587-608页

作者： Xueman Chen Erwei Song Guangdong Provincial Key laboratory of Malignant tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510120P.R.China Breast tumor Center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510120P.R.China

Cancer cells can be conceived as“living organisms”interacting with cellular or non-cellular components in the host internal environment,not only the local tumor microenvironment but also the distant organ niches,as well as the immune,nervous and endocrine systems,to construct a self-sustainable tumor *** increasing evidence for the systemic tumor-host interplay,we predict that a new era of cancer therapy targeting the ecosystemic vulnerability of human malignancies has *** around the tumor ecosystem scoped as different hierarchies of primary,regional,distal and systemic onco-spheres,we comprehensively review the tumor-host interaction among cancer cells and their local microenvironment,distant organ niches,immune,nervous and endocrine systems,highlighting material and energy flow with tumor ecological homeostasis as an internal driving *** also substantiate the knowledge of visualizing,modelling and subtyping this dynamically intertwined networkwith recent technological advances,and discuss ecologically rational strategies formore effective cancer therapies.

关键词： ecological therapy neuroendocrine system onco-sphere tumor-host interplay pre-metastatic niche tumor ecosystem tumor immunity tumor microenvironment

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Dual-function baicalin and baicalin-loaded poly（lactic-co-glycolic acid） nanoparticles： Immune activation of dendritic cells and arrest of the melanoma cell cycle at the G2/M phase

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Particuology 2018年第2期16卷 64-71页

作者： Huimei Wang Shulan Han Lianyan Wang Tingyuan Yang Guifeng Zhang Lian Yu Yue Zhao Key laboratory of Forest Plant Ecology Ministry of Education Northeast Forestry University Harbin 150040 China National Key laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing 100190 China College of PharmacyJiamusi University Jiamusi 154000 China Epithelial systems Biology laboratory Systems Biology Center National Heart Lung and Blood Institute National Institutes of Health Bethesda MD 20892-1603. USA

Accumulating evidence suggests that the flavone glycoside baicalin has immunomodulatory effects and antitumor potential. However, its weak stability in solution, poor absorption, and low bioavailability limit its clinical application. To overcome these disadvantages, we developed baicalin-loaded poly（lactic-co-glycolic acid） nanoparticles （PLGA-B） of small size. Next, we evaluated the dual function of immunotherapy and chemotherapy for PLGA-B using immune-related cells and tumor cells. Results showed that PLGA-B were spherical, with a particle size -120 nm and narrow size distribution with an excellent polydispersity index of 0.103. In vitro experiments revealed that baicalin and PLGA-B could activate dendritic cells （DCs） to have higher expression of surface marker molecules and costimulatory molecules than those of control cells. Baicalin and PLGA-B could trigger apoptosis in melanoma （B16） cells via cell-cycle arrest at the G2/M phase. These data suggest that PLGA-B have important roles in activating DCs and killing melanoma cells. Our study could lay a foundation for melanoma treatment through a combined strategy of immunotherapy and chemotherapy.

关键词： Baicalin Baicalin-loaded PLGA nanoparticles Dendritic cells activation Anti-tumor

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Influence of Wallach’s Rule on Chiral AIE systems and Its Application in Cryptographic Information Storage

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CCS Chemistry 2022年第12期4卷 3686-3692页

作者： Qiu Chen Peng Xi Ming Luo Yu Jing Qin Ting Wang Bing Bai Xi Long Wei Kai Li Shuang Quan Zang Henan Key laboratory of Crystalline Molecular Functional Materials Henan International Joint Laboratory of Tumor Theranostical Cluster MaterialsGreen Catalysis CenterCollege of ChemistryZhengzhou UniversityZhengzhou 450001

Aggregation-induced emission luminogens(AIEgens)exhibit excellent luminescence properties in the aggregated *** chiral AIEgens,a combination of right-and left-handed objects can be packed more tightly than homochiral objects due to Wallach’s ***,the manner in which Wallach’s rule can affect the luminescence properties of chiral AIEgens remains *** report that,in contrast to their homochiral counterparts,racemic AIEgens obtained using binaphthyl-2,2′-diamine salicylaldehyde Schiff-bases(BINAPAS)exhibit racemism-enhanced *** was found that the intramolecular motion of racemic BINAPAS is more restricted than that of chiral BINAPAS due to its denser packing mode,which significantly enhances the emission intensity of racemic *** on this finding,a novel single-molecule cryptographic information storage system was *** work offers a new perspective for understanding the influence of Wallach’s rule on the aggregationinduced emission properties of organic molecules,and more importantly,extends Wallach’s rule to the fundamental difference in chiral-photophysics.

关键词： aggregation-induced emission Wallach’s rule chiral-photophysics

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A biomimetic antitumor nanovaccine based on biocompatible calcium pyrophosphate and tumor cell membrane antigens

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Asian Journal of Pharmaceutical Sciences 2021年第1期16卷 97-109页

作者： Minghui Li Mengmeng Qin Ge Song Hailiang Deng Dakuan Wang Xueqing Wang Wenbing Dai Bing He Hua Zhang Qiang Zhang Beijing Key laboratory of Molecular Pharmaceutics and New Drug Delivery systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Currently,the cancer immunotherapy has made great progress while antitumor vaccine attracts substantial ***,the selection of adjuvants as well as antigens are always the most crucial issues for better *** this study,we proposed a biomimetic antitumor nanovaccine based on biocompatible nanocarriers and tumor cell membrane ***,endogenous calcium pyrophosphate nanogranules with possible immune potentiating effect are designed and engineered,both as delivery vehicles and ***,these nanocarriers are coated with lipids and B16-OVA tumor cell membranes,so the biomembrane proteins can serve as tumor-specific *** was found that calcium pyrophosphate nanogranules themselves were compatible and possessed adjuvant effect,while membrane proteins including tumor associated antigen were transferred onto the *** was demonstrated that such a biomimetic nanovaccine could be well endocytosed by dendritic cells,promote their maturation and antigen-presentation,facilitate lymph retention,and trigger obvious immune *** was confirmed that the biomimetic vaccine could induce strong T-cell response,exhibit excellent tumor therapy and prophylactic effects,and simultaneously possess nice *** general,the present investigation might provide insights for the further design and application of antitumor vaccines.

关键词： Biomimetic nanovaccine Calcium pyrophosphate Membrane antigens tumor immunotherapy Adjuvant

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Numerical modeling and simulation of temperature distribution uncertainty subject to ferromagnetic thermoseeds hyperthermia

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Chinese Science Bulletin 2014年第12期59卷 1317-1325页

作者： Zi-Han Zhuo Jie Wang Wei-Ming Zhai Heng Wang Jin-Tian Tang Key laboratory Particle & Radiation Imaging Ministry of Education Department of Engineering Physics Tsinghua University State Key laboratory of Intelligent Technology and systems National Laboratory for Information Science and TechnologyDepartment of Computer Science and Technology Tsinghua University

In the process of ferromagnetic thermoseeds mediated magnetic induction hyperthermia,the temperature distribution in the tumor region is a key factor to determine the therapy *** the preoperative treatment planning,discrepancies of the treatment parameters may lead to the temperature distribution uncertainty within the target *** prediction of temperature distribution may induce the treatment failure;therefore,it would be significant to investigate the uncertainty of tissue temperature prediction caused by the disturbance of calculation *** this paper,3D temperature field and necrosis zone of tissues in ferromagnetic thermoseeds hyperthermia are simulated by the finite volume algorithm,and effects of parameter uncertainties on the temperature distribution are *** show that selecting appropriate magnetic field parameters for treatment is a priority to guarantee therapeutic *** properties and blood perfusion rate are the obvious disturbing terms for temperature distribution,while the metabolic heat of bio-tissues can often be ignored within *** investigation is of importance for guiding reasonable and optimal preoperative treatment planning.

关键词：参数不确定性温度分布算法模拟磁疗法热疗数值模型治疗效果铁

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Enhanced stability and efficacy of GEM-TOS prodrug by co-assembly with antimetastatic shell LMWH-TOS

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Acta Pharmaceutica Sinica B 2020年第10期10卷 1977-1988页

作者： Rong Guoy Yang Longy Zhengze Lu Miao Deng Penghui He Man Li Qin He Key laboratory of Drug Targeting and Drug Delivery systems of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610064China

Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their ***,prodrug strategy was *** some prodrugs are still with poor solubility or stability,a synergy strategy is needed to enhance their ***(GEM)is a prescribed anticancer drug,however,the rapid clearance,growing resistance and serious side effects limit its clinical *** GEM with D-a-tocopherol succinate(TOS)is an effective solution,while the GEM-TOS(GT)is unstable in aqueous solution.D-a-Tocopherol polyethylene glycol succinate(TPGS)has been used to enhance the stability,but GT stabilized by TPGS(GTT)has limited effect on tumor *** metastases lead to high mortality in patients suffering from *** order to further achieve antimetastatic effect,an amphiphilic polymer(LT)was synthesized by connecting low-molecular-weight heparin(LMWH)with TOS,and eventually obtained desired selfdelivery micellar NPs(GLT)by co-assembly GT with *** GLT not only possessed excellent stability,but also inhibited the metastases by acting on different phases of the metastatic *** hydrophobic TOS inhibited the secretion of matrix metalloproteinase-9(MMP-9),the hydrophilic LMWH inhibited the interaction between tumor cells and *** a result,GLT reduced tumor cells entering the blood and implanting at the distant organs,leading to a much more excellent inhibitory effect on the lung metastasis than GEM and GTT.

关键词： Gemcitabine TOS LMWH tumor metastasis MMP-9

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Restoration of electrical microenvironment enhances bone regeneration under diabetic conditions by modulating macrophage polarization

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Bioactive Materials 2021年第7期6卷 2029-2038页

作者： Xiaohan Dai Boon Chin Heng Yunyang Bai Fuping You Xiaowen Sun Yiping Li Zhangui Tang Mingming Xu Xuehui Zhang Xuliang Deng Hunan Key laboratory of Oral Health Research&Hunan 3D Printing Engineering Research Center of Oral Care&Hunan Clinical Research Center of Oral Major Diseases and Oral Health&Xiangya Stomatological Hospital&Xiangya School of Stomatology Central South UniversityChangsha410008PR China Department of Dental Materials&Dental Medical Devices Testing Center Peking University School and Hospital of StomatologyBeijing100081PR China Department of Geriatric Dentistry Peking University School and Hospital of StomatologyBeijing100081PR China Central laboratory Peking University School and Hospital of StomatologyBeijing100081PR China Institute of systems Biomedicine Department of ImmunologySchool of Basic Medical SciencesBeijing Key Laboratory of Tumor Systems BiologyPeking University Health Science CenterBeijing100191PR China National Engineering laboratory for Digital and Material Technology of Stomatology NMPA Key Laboratory for Dental MaterialsBeijing Laboratory of Biomedical Materials&Beijing Key Laboratory of Digital StomatologyPeking University School and Hospital of StomatologyBeijing100081PR China

Macrophage-mediated inflammation compromises bone repair in diabetic *** signaling cues are known to regulate macrophage ***,the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be *** the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO_(3)/poly(vinylidene fluoridetrifluoroethylene)(BTO/P(VDF-TrFE))nanocomposite *** vitro,the polarized BaTiO_(3)/poly(vinylidene fluoridetrifluoroethylene)(BTO/P(VDF-TrFE))nanocomposite membranes inhibited high glucose-induced M1-type inflammation,by effecting changes in cell morphology,M1 marker expression and pro-inflammatory cytokine secretion in *** led to enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells(BM-MSCs).In vivo,the biomimetic electrical microenvironment recapitulated by the polarized nanocomposite membranes switched macrophage phenotype from the pro-inflammatory(M1)into the pro-healing(M2)phenotype,which in turn enhanced bone regeneration in rats with type 2 diabetes *** studies revealed that the biomimetic electrical microenvironment attenuated pro-inflammatory M1 macrophage polarization under hyperglycemic conditions by suppressing expression of AKT2 and IRF5 within the PI3K-AKT signaling pathway,thereby inducing favorable osteo-immunomodulatory *** study thus provides fundamental insights into the biological effects of restoring the electrical microenvironment conducive for osteogenesis under DM conditions,and offers an effective strategy to design functionalized biomaterials for bone regeneration therapy in diabetic patients.

关键词： Electrical microenvironment Diabetes Ferroelectric nanocomposites Bone regeneration Macrophage polarization

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A systematic survey of LU domain-containing proteins reveals a novel human gene,LY6A,which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

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Frontiers of Medicine 2023年第3期17卷 458-475页

作者： Dan Liu Chunhui Xu Yanting Liu Wen Ouyang Shaojian Lin Aining Xu Yuanliang Zhang Yinyin Xie Qiuhua Huang Weili Zhao Zhu Chen Lan Wang Saijuan Chen Jinyan Huang Zhe Bao Wu Xiaojian Sun Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Key laboratory of systems Biomedicine Ministry of EducationShanghai Center for Systems BiomedicineShanghai Jiao Tong UniversityShanghai 200240China CAS Key laboratory of Tissue Microenvironment and tumor Shanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Department of Neurosurgery Center of Pituitary TumorRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Biomedical Big Data Center First Affiliated HospitalZhejiang University School of Medicineand Cancer CenterZhejiang UniversityHangzhou 310000China Department of Neurosurgery First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China

The Ly-6 and uPAR(LU)domain-containing proteins represent a large family of cell-surface *** particular,mouse Ly-6A/Sca-1 is a widely used marker for various stem cells;however,its human ortholog is *** this study,based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins,we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/*** gene,hereby named LY6A,reversely overlaps with a lncRNA gene in the majority of exonic *** found that LY6A is aberrantly expressed in pituitary tumors,but not in normal pituitary tissues,and may contribute to *** to mouse Ly-6A/Sca-1,human LY6A is also upregulated by interferon,suggesting a conserved transcriptional regulatory mechanism between humans and *** cloned the full-length LY6A cDNA,whose encoded protein sequence,domain architecture,and exon‒intron structures are all well conserved with mouse Ly-6A/*** expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell ***,these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

关键词： LU domain-containing protein family novel human gene LY6A pituitary tumor biomarker nonsynonymous SNP GPI-anchored protein

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