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cell membrane-coated nanoparticles for immunotherapy

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Chinese Chemical Letters 2022年第4期33卷 1673-1680页

作者： Hang Liu Zhaohua Miao Zhengbao Zha School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China

Nanoparticle-based disease detection, prevention and therapies have gained increased interests in biomedical applications, owing to their significant advantages in therapeutic efficacy and safety. Nonetheless, suffering from the challenges including fast recognition and clearance of foreign nanoparticles by innate immune system before arriving at diseased regions, clinical applications of nanoparticles are usually intercepted. Among various strategies for reducing non-specific phagocytosis and enhancing diseasetargeting efficiency of nanoparticles, membrane coating nanotechnology exhibits great potential in the disease diagnosis and therapeutics due to both the structural and functional preservation of membrane proteins from source cells. Benefiting the inherited immune-regulation capacities, this review mainly summarized the latest development of such biomimetic nanoparticles for immunotherapy in treating immune-related diseases including microbial infections, inflammation, tumor and autoimmune diseases.

关键词： Biomimetic nanoparticles Immunotherapy Nanovaccine cell membrane

cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment

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Acta Pharmaceutica Sinica B 2018年第1期8卷 14-22页

作者： Ruixiang Li Yuwei He Shuya Zhang Jing Qin Jianxin Wang Department of Pharmaceutics School of Pharmacy Fudan University Key Laboratory of Smart Drug Delivery Ministry of Education Institute of Materia Medica Academy of Chinese and Western Integrative Medicine Fudan University

Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems(fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles(CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.

关键词： cell membrane Biomimetic nanoparticle Drug delivery Cancer targeting Circulation Molecular recognition

Coarse grained molecular dynamics and theoretical studies of carbon nanotubes entering cell membrane

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Acta Mechanica Sinica 2008年第2期24卷 161-169页

作者： Xinghua Shi Yong Kong H. Gao Division of Engineering Brown University 182 Hope Street Providence RI 02912 USA ICx Radiation GmbH Koelnerstrasse 99 42651 Solingen Germany

Motivated by recent experimental observations that carbon nanotubes （CNT） can enter animal cells, here we conduct coarse grained molecular dynamics and theoretical studies of the intrinsic interaction mechanisms between CNT＇s and lipid bilayer. The results indicate that CNT-cell interaction is dominated by van der Waals and hydrophobic forces, and that CNT＇s with sufficiently small radii can directly pierce through cell membrane while larger tubes tend to enter cell via a wrapping mechanism. Theoretical models are proposed to explain the observed size effect in transition of entry mechanisms.

关键词： Molecular dynamics Carbon nanotube cell membrane Interaction mechanism

cell membrane sample preparation method of combined AFM and dSTORM analysis

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Biophysics Reports 2022年第4期8卷 183-192页

作者： Mingjun Cai Huili Wang Guanfang Zhao Hongru Li Jing Gao Hongda Wang University of Science and Technology of China State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences Laboratory for Marine Biology and Biotechnology Pilot National Laboratory for Marine Science and Technology (Qingdao)

A major role of cell membranes is to provide an ideal environment for the constituent proteins to perform their biological functions. A deep understanding of the membrane proteins assembly process under physiological conditions is quite important to elucidate both the structure and the function of the cell membranes. Along these lines, in this work, a complete workflow of the cell membrane sample preparation and the correlated AFM and dSTORM imaging analysis methods are presented. A specially designed, angle-controlled sample preparation device was used to prepare the cell membrane *** correlated distributions of the specific membrane proteins with the topography of the cytoplasmic side of the cell membranes can be obtained by performing correlative AFM and dSTORM measurements. These methods are ideal for systematically studying the structure of the cell membranes. The proposed method of the sample characterization was not only limited to the measurement of the cell membrane but also can be applied for both biological tissue section analysis and detection.

关键词： Atomic force microscopy (AFM) Super-resolution microscopy (SRM) Direct stochastic optical reconstruction microscopy (dSTORM) cell membrane Combined technique

Tumor cell membrane remodeling with universal ligand for CAR-T cells to inhibit solid tumors

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Science China Chemistry 2023年第11期66卷 3223-3231页

作者： Jin-Xuan Fan Zhong-Bao Hu Hui-Yun Gu Wen-Qiang Qu Wen Li Bai-Wen Qi Ai-Xi Yu Xian-Zheng Zhang Key Laboratory of Biomedical Polymers of Ministry of Education Department of ChemistryWuhan UniversityWuhan 430072China Department of Orthopedic Trauma and Microsurgery ZhongNan Hospital of Wuhan UniversityWuhan 430071China

Heterogeneity is a major obstacle to the success of CAR-T therapy in treating solid tumors. The complex tumor micro-environment and varying phenotypes of tumor cells might result in antigen escape, drug resistance, and tumor recurrence. To address this issue, we proposed to use lipid-modified fluorescein isothiocyanate(Lip-FITC) as an artificial ligand to normalize the phenotypes of solid tumor cells. In murine cutaneous melanoma and colon adenocarcinoma that prefer to utilize exogenous long-chain fatty acids, we observed much more uptake of Lip-FITC and significantly increased FITC fluorescence on tumor cell membranes than normal cells. This specific exogenous labeling with FITC enhanced the recognition and selectivity of CART cells in solid tumors, bypassing the limitations derived from antigen expression differences in adoptive cell therapies. Lipid metabolism analysis and in vitro experiments demonstrated the sufficient uptake of long-chain fatty acid(LCFAs)-modified Lip-FITC by solid tumor cells, as well as satisfactory ligand assembly on cell membranes. In solid tumor model, the treatment induced the recognition and initiation of CART cells and successfully suppressed tumor progression through T-cell immunity.

关键词： cell membrane CAR-T therapy immune response tumor heterogeneity long-chain fatty acid

Monitoring of cell membrane Microenvironment Based on DNA Nanodevices

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Chemical Research in Chinese Universities 2024年第2期40卷 255-267页

作者： NAN Hexin CAI Ming KUANG Shi NIE Zhou State Key Laboratory of Chemo/Biosensing and Chemometrics College of Chemistry and Chemical EngineeringHunan Provincial Key Laboratory of Biomacromolecular Chemical BiologyHunan UniversityChangsha410082P.R.China

The cell membrane is a critical barrier for cellular homeostasis,integral to signaling and intercellular communication,and vital for understanding cellular functions and disease *** its microenvironment is crucial for uncovering the molecular basis of physiological and pathological processes associated with the cell membrane,driving the development of bioanalytical toolkits capable of dynamically monitoring the cell surface *** the continuous advancement of functional nucleic acids and dynamic DNA nanotechnology,DNA nanodevices with controllable nanosized geometry,specific molecular recognition,and selective membrane-localization properties offer a versatile platform for probing the cell membrane *** this review,we summarize the current biosensing and membrane-anchoring mechanisms of DNA nanodevices and highlight their use in studying key cell membrane events,including membrane lipid dynamics,transmembrane transport,receptor dimerization,and signal ***,we discuss the challenges and potential future applications of DNA nanodevices in advancing cell membrane biology research and biomedical applications.

关键词： DNA nanodevice cell membrane cellular micro-environment Monitoring

Natural killer cell membrane doped supramolecular nanoplatform with immuno-modulatory functions for immuno-enhanced tumor phototherapy

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Chinese Chemical Letters 2024年第10期35卷 205-212页

作者： Ying Gao Rong Zhou Qiwen Wang Shaolong Qi Yuanyuan Lv Shuang Liu Jie Shen Guocan Yu Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou 310015 China Department of Cardiology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China MOE Key Laboratoryof Bioorganic Phosphorus Chemistry & Chemical Biology Department of ChemistryTsinghua UniversityBeijing04Chin Emergency Department State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China

Photodynamic therapy(PDT)has garnered significant attention as a promising approach to cancer therapy,harnessing the combined benefits of localized light treatment and the accompanying host immune *** this study,we engineered an immuno-enhanced PDT nanoplatform,denoted as HM@p-MOF(hybrid membrane@porphyrin-metal organic framework).The core porphyrin-MOF was cloaked with a hybrid membrane derived from B16F10 cancer cells and NK cells,resulting in enhanced *** both in vitro and in vivo experiments,our finding demonstrated that the hybrid membrane conferred dual targeting capabilities to the nanoplatform,leveraging the unique properties of the B16F10 membrane and NK membrane to augment immunogenic cell death(ICD)induced by photodynamic ***,in conjunction with the immunomodulatory functions of the NK cell membrane,we observed an expansion of in situ immune infiltration leading to a systemic immune *** HM@p-MOF nanoplatform exhibited the capacity to not only inhibit the growth of mouse melanoma but also suppress *** innovative HM@p-MOF nanoplatform present a viable strategy to enhance phototherapeutic efficacy for both localized and metastatic *** provides a direction for the fabrication of biomimetic nanomedicines possessing immuno-modulatory function.

关键词： Biomimetic cell membrane Metal-organic framework Phototherapy Tumor targeting

Quinacrine pretreatment reduces microwave-induced neuronal damage by stabilizing the cell membrane

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Neural Regeneration Research 2018年第3期13卷 449-455页

作者： Xue-feng Ding Yan Wu Wen-rui Qu Ming Fan Yong-qi Zhao Department of Cognitive Sciences Beijing Institute of Basic Medical Sciences Hand & Foot Surgery and Reparative & Reconstructive Surgery Center Orthopedic Hospital of the Second Hospital of Jilin University

Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine （20 and 40 mM） and irradiated them with 50 mW/cm^2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation.

关键词： nerve regeneration quinacrine microwave irradiation heat shock cell apoptosis cell necrosis thermal effect cell membrane heat shock protein 70 nerve cells neural regeneration

A tumor cell membrane-coated self-amplified nanosystem as a nanovaccine to boost the therapeutic effect of anti-PD-L1 antibody

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Bioactive Materials 2023年第3期21卷 299-312页

作者： Zhilin Li Hao Cai Zhiqian Li Long Ren Xuelei Ma Hongyan Zhu Qiyong Gong Hu Zhang Zhongwei Gu Kui Luo Laboratory of Stem cell Biology Department of RadiologyHuaxi MR Research Centner(HMRRC)Department of BiotherapyCancer CenterNational Clinical Research Center for GeriatricsFrontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China Amgen Bioprocessing Centre Keck Graduate InstituteClaremontCA91711USA Functional and Molecular Imaging Key Laboratory of Sichuan Province And Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu610041China

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosup-pressive cancers like triple-negative breast cancer(TNBC),induction of immunogenic cell death(ICD)at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint ***,a self-amplified biomimetic nanosystem,mEHGZ,was constructed by encapsulation of epirubicin(EPI),glucose oxidase(Gox)and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin(CRT)over-expressed tumor cell *** acts as an ICD inducer,Gox and hemin medicate the cascade generation of reactive oxygen species(ROS)to strengthen the ICD effect,and CRT-rich membrane as“eat me”signal promote presentation of the released antigens by dendritic cells(DCs)to invoke the tumor-immunity *** biomimetic delivery system displays an amplified ICD effect via Gox oxidation,hydroxyl radical generation and glutathione(GSH)*** induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes(CTLs)infiltration,reversing an immunosuppressive tumor microenvironment to an immunoresponsive *** with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis,supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 *** self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

关键词： cell membrane Biomimetic nanosystem Immunogenic cell death Immunotherapy anti-PD-L1 antibody