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Monomethyl fumarate augments NK cell lysis of tumor cells through degranulation and the upregulation of NKp46 and CDIO7a

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Cellular & Molecular Immunology 2016年第1期13卷 57-64页

作者： Heidi Vego Kristin L Sand Rune A Hoglund Lars-Egil Fallang Glenn Gundersen Trygve Holmoy Azzam A Maghazachi Departmentof Physiology Institute of Medical Basic Sciences University of Oslo Oslo Norway Medical Department Biogen Idec Norway AS OsloNorway Department of Neurology Akershus University Hospital and institute of Clinical Medicine University of Oslo Oslo Norway

Dimethyl fumarate （DMF） is a new drug used to treat multiple sclerosis （MS） patients. Here, we examined the effects of DMF and the DMF metabolite monomethyl fumarate （MMF） on various activities of natural killer （NK） cells. We demonstrated that MMF augments the primary CD56^＋, but not CD56^-, NK cell lysis of K562 and RAJI tumor cells. MMF induced NKp46 expression on the surface of CD56^＋, but not CD56^-, NK cells after incubation for 24 h. This effect was closely correlated with the upregulation of CD107a expression on the surface of CD56＋ NK cells and the induction of Granzyme B release from these cells through this metabolite. An anti-NKp46 antibody inhibited the MMF-induced upregulation of CD107a and the lysis of tumor cells through CD56^＋ NK cells. Thus, these results are the first to show that MMF augments CD56^＋ NK cell lysis of tumor target cells, an effect mediated through NKp46. This novel effect suggests the use of MMF for therapeutic and/or preventive protocols in cancer.

关键词： cancer prevention cancer treatment CDlO7a cytotoxicity dimethyl fumarate Granzyme B monomethyl fumarate natural killer cells NKp46

STING-activating drug delivery systems:Design strategies and biomedical applications

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Chinese Chemical Letters 2021年第5期32卷 1615-1625页

作者： Chunying Li Yifan Zhang Yilin Wan Jingle Wang Jing Lin Zhiming Li Peng Huang Department of Dermatology and Venereology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China Marshall Laboratory of Biomedical Engineering International Cancer CenterLaboratory of Evolutionary Theranostics(LET)School of Biomedical EngineeringShenzhen University Health Science CenterShenzhen 518060China Department of Medical Oncology The Third Affiliated Hospital of Shanghai UniversityWenzhou 325000China

The stimulator of interferon genes(STING)shows promising clinical activity in infectious diseases and ***,the lack of targeting capability and intracellular stability of STING agonists severely limits the therapeutic ***,drug delivery systems(DDSs)overcome these delivery barriers of STING agonists via passive or active cell targeting,prolonged blood circulation and drug release,and lysosome escape,*** this review,we will describe in detail how existing DDSs are designed to overcome delivery barriers and activate the STING pathway,and the current biomedical applications of STING-activating DDSs in the treatments of infectious diseases and ***,the prospects and challenges of DDSs in STING activation are discussed.

关键词： STING agonist Drug delivery system cancer treatment Anti-virus treatment Immunotherapy

Gonadal damage and options for fertility preservation in female and male cancer survivors

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Asian Journal of Andrology 2006年第5期8卷 515-533页

作者： Theodoros Maltaris Heinz Koelbl Rudolf Seufert Franklin Kiesewetter Matthias W. Beckmann Andreas Mueller Ralf Dittrich Department of Obstetrics and Gynecology Johannes Gutenberg University Mainz D-55124 Germany Division of Andrology Erlangen University Hospital University of Erlangen-Nuremberg Erlangen Germany Department of Obstetrics and Gynecology Erlangen University Hospital University of Erlangen-Nuremberg Erlangen Germany

It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization （IVF） after cancer treatment are also presented.

关键词： reproduction cryopreservation male infertility semen preservation fertility preservation cancer treatment ovarian tissue

Functional organic nanoparticles for photodynamic therapy

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Chinese Chemical Letters 2016年第8期27卷 1412-1420,1470页

作者： Lei-Lei Rui Hong-Liang Cao Yu-Dong Xue Li-Chao Liu Lei Xu Yun Gao Wei-An Zhang Shanghai Key Laboratory of Advanced Polymeric Materials East China University of Science and Technology

In recent years,cancer has been one of the leading causes of death in the *** effort has been devoted to developing cancer *** therapy（PDT） is a noninvasive therapeutic modality by combining the light of a specific wavelength,a photosensitizer（PS） and oxygen,which has been widely applied for the treatment of ***,the application of PDT in clinic is greatly limited due to lack of tumor selectivity and often causing skin *** use of organic nanoparticles（NPs） as an advanced technology in the field of PDT shows a great promise to overcome these ***,in this review,we summarize several functional organic NPs as PS carriers that have been developed to enhance the efficacy of PDT against cancers.

关键词： Photosensitizers Photodynamic therapy Organic nanoparticles Singlet oxygen cancer treatment

Recent advances in drug delivery systems for targeting cancer stem cells

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Acta Pharmaceutica Sinica B 2021年第1期11卷 55-70页

作者： Hongxia Duan Yanhong Liu Zhonggao Gao Wei Huang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Department of PharmaceuticsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem *** few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation *** addition,CSCs have the ability to escape immune ***,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after ***,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under *** the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being *** this review,we summarize the advances in CSC-targeted ***,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.

关键词： cancer stem cells Targeting strategies Drug delivery systems cancer treatment Niche Biomarker Cellular level Molecular level

Functional Electrospun Fibers for Local Therapy of cancer

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Advanced Fiber Materials 2020年第5期2卷 229-245页

作者： Jingwen Zhao Wenguo Cui Shanghai Key Laboratory for Prevention and treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai 200025People’s Republic of China

Despite great efforts and advancement in the treatment of cancer,tumor recurrence and metastasis remain significant challenges and demand novel therapy ***,advances in biomaterials and drug delivery systems have facilitated the development of the local therapy of cancer,among which electrospun nanofibrous scaffolds show great promise owing to their porous structure,relatively large surface area,high drug loading capacity,similarity with the native extracellular matrix,and possibility of the combination of various ***,we review this rapidly developing field of electrospun nanofibrous scaffolds as a drug delivery system for cancer local therapy,in particular addressing stimuli-responsive drug release,as well as its combination with stem cell and immune *** and future perspectives are also discussed.

关键词： Electrospinning cancer treatment Local therapy Drug delivery Stimuli-responsive

Effect of physicochemical properties on in vivo fate of nanoparticle-based cancer immunotherapies

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Acta Pharmaceutica Sinica B 2021年第4期11卷 886-902页

作者： Yongchao Wang Jinjin Wang Dandan Zhu Yufei Wang Guangchao Qing Yuxuan Zhang Xiaoxuan Liu Xing-Jie Liang State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases Center of Drug DiscoveryCenter of Advanced Pharmaceutics and BiomaterialsChina Pharmaceutical UniversityNanjing 210009China Laboratory of Controllable Nanopharmaceuticals Chinese Academy of Sciences(CAS)Center for Excellence in Nanoscience and CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Current advances of immunotherapy have greatly changed the way of cancer *** the same time,a great number of nanoparticle-based cancer immunotherapies(NBCIs)have also been explored to elicit potent immune responses against ***,few NBCIs are nearly in the clinical trial which is mainly ascribed to a lack understanding of in vivo fate of nanoparticles(NPs)for cancer *** for cancer immunotherapy mainly target the immune organs or immune cells to enable effcient antitumor immune *** physicochemical properties of NPs including size,shape,elasticity and surface properties directly affect their interaction with immune systems as well as their in vivo fate and therapeutic ***,systematic analysis of the physicochemical properties and their effect on in vivo fate is urgently *** this review,we frst recapitulate the fundamentals for the in vivo fate of NBCIs including physio-anatomical features of lymphatic system and strategies to modulate immune ***,we highlight the effect of physicochemical properties on their in vivo fate including lymph nodes(LNs)drainage,cellular uptake and intracellular *** and opportunities for rational design of NPs for cancer immunotherapy are also discussed in detail.

关键词： Physicochemical properties Nanoparticle-based cancer immunotherapies cancer treatment In vivo fate Immune responses Lymph nodes drainage Cellular uptake Intracellular transfer

Advances of therapeutic microbubbles and nanobubbles

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National Science Open 2023年第5期2卷 113-126页

作者： Bin Huang Li Yang Wenbing Yu Yan Li Ling Li Ning Gu State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Science and Medical Engineering Southeast University School of Biomedical Engineering and Informatics Nanjing Medical University Zhongda Hospital Southeast University Medical School Nanjing University

As versatile nanotools, microbubbles(MBs) and nanobubbles(NBs) have gained increasing attention because of their great potentials for therapeutic applications. The filled gases can greatly influence the physical properties of the MBs and NBs, such as size, zeta potential, and stability. Importantly, the biological activity of the filled gases plays a key role in the therapeutic effect of MBs and NBs. In this review, we will introduce the background, classification, and design strategies of therapeutic MBs and NBs based on bio-active and bio-inactive gases. Furthermore, focus will be placed on the biomedical applications in cancer treatments, including drug delivery, targeting effect and combinations of different therapeutic ***, we will discuss the remaining challenges and future perspectives of therapeutic MBs and NBs.

关键词： microbubbles nanobubbles gas cancer treatment ultrasound

Interactome Analysis of Microtubule-targeting Agents Reveals Cytotoxicity Bases in Normal Cells

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Genomics, Proteomics & Bioinformatics 2017年第6期15卷 352-360页

作者： Andres Julian Gutierrez-Escobar Gina Mendez-Callejas Grupo de Investigaciones Biomedicas y Genetica Aplicada-GIBGA Universidad de Ciencias Aplicadas y Ambientales U.D.C.A.Bogota 111166Colombia

cancer causes millions of deaths annually and microtubule-targeting agents （MTAs） are the most commonly-used anti-cancer drugs. However, the high toxicity of MTAs on normal cells raises great concern. Due to the non-selectivity of MTA targets, we analyzed the interaction net- work in a non-cancerous human cell. Subnetworks of fourteen MTAs were reconstructed and the merged network was compared against a randomized network to evaluate the functional rich- ness. We found that 71.4% of the MTA interactome nodes are shared, which affects cellular pro- cesses such as apoptosis, cell differentiation, cell cycle control, stress response, and regulation of energy metabolism. Additionally, possible secondary targets were identified as client proteins of interphase microtubules. MTAs affect apoptosis signaling pathways by interacting with client pro- teins of interphase microtubules, suggesting that their primary targets are non-tumor cells. The paclitaxel and doxorubicin networks share essential topological axes, suggesting synergistic effects. This may explain the exacerbated toxicity observed when paclitaxel and doxorubicin are used in combination for cancer treatment.

关键词： cancer treatment Microtubule-targeting agentInteractome analysis cancer biology Apoptosis