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pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

Acta Pharmaceutica Sinica B 2024年第2期14卷 781-794页

作者： Shuai Guo Chunhui Li Changrong Wang Xiaowen Cao Xinyue Liu xing-jie liang Yuanyu Huang Yuhua Weng School of Medical Technology Advanced Research Institute of Multidisciplinary ScienceSchool of Life ScienceKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China School of Pharmacy Shandong New Drug Loading&Release Technology and Preparation Engineering LaboratoryBinzhou Medical UniversityYantai 264003China School of Ophthalmology and Optometry School of Biomedical EngineeringThe Eye HospitalWenzhou Medical UniversityWenzhou 325027China Chinese Academy of Sciences(CAS) Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China

Small interfering RNA(siRNA)has a promising future in the treatment of ocular diseases due to its high efficiency,specificity,and low toxicity in inhibiting the expression of target genes and ***,due to the unique anatomical structure of the eye and various barriers,delivering nucleic acids to the retina remains a significant *** this study,we rationally design PACD,an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block(A),a siRNA binding block(B)and a pH-responsive block(C).PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple *** evaluating its pH-responsive activity,gene silencing efficiency in retinal cells,intraocular distribution,and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis,we demonstrate the efficiency and safety of PACD in delivering siRNA in the *** are surprised to discover that,the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency,excellent gene silencing,and inhibit retinal *** study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

关键词： SiRNA Oculardeliverysystem Block polymer Endosomalescape Retinal neovascularization Blood-retinal barrier VEGFA Safety

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The p38/MAPK pathway as a therapeutic target to prevent therapeutic escape of breast cancer stem cells

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Science China(Life Sciences) 2024年第9期67卷 1867-1880页

作者： Weixiao Yan Xiaotong Wang Wenjing Wang Qi Guo Na Huang Hao Chen xing-jie liang Yu Han Dandan Liu Jinchao Zhang State Key Laboratory of New Pharmaceutical Preparations and Excipients/Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education/College of Chemistry and Materials Science Chemical Biology Key Laboratory of Hebei ProvinceHebei UniversityBaoding 071002China CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety National Center for Nanoscience and TechnologyBeijing 100190China

Cancer stem cells(CSCs)play an important role in metastasis development,tumor recurrence,and treatment resistance,and are essential for the eradication of ***,therapies fail to eradicate CSCs due to their therapeutic stress-induced cellular escape,which leads to enhanced aggressive behaviors compared with CSCs that have never been ***,the underlying mechanisms regulating the therapeutic escape remain *** this end,we established a model to isolate the therapeutic escaped CSCs(TSCSCs)from breast CSCs and performed the transcription profile to reveal the ***,we demonstrated that the behavior of therapeutic escape was regulated through the p38/MAPK signaling pathway,resulting in TSCSCs exhibiting enhanced motility and ***,blocking the p38/MAPK signaling pathway effectively reduced motility and metastasis ability both in vitro and in vivo,which were further supported by downregulated motility-related genes and epithelial-mesenchymal transition(EMT)-related proteins vimentin and *** obtained findings reveal the p38/MAPK pathway as a potential therapeutic target for TSCSCs and would provide profound implications for cancer therapy.

关键词： therapeutic escape breast cancer stem cells motility p38/MAPK signaling pathway molecular mechanism

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Precise nano-programmed ferroptosis with enhanced tumor chemotherapy

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中国科学：材料科学（英文版） 2020年第10期63卷 2086-2088页

作者： xing-jie liang College of Nanoscience and Technology University of Chinese Academy of SciencesBeijing 100049China Laboratory of Controllable Nanopharmaceuticals CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and Technology of ChinaChinese Academy of Sciences(CAS)Beijing 100190China CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of ChinaBeijing 100190China

Cancer treatment is one of the greatest challenges in biomedical research,and the development of novel tumor-inhibition mechanisms has long been a topic of interest for researchers in this *** is one such candidate that holds promise for clinical *** is a recently discovered non-apoptotic model of regulated cell death that shows high iron-dependence.

关键词： Cancer clinical chemotherapy

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Nanomaterial-assisted sensitization of oncotherapy

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Nano Research 2018年第6期11卷 2932-2950页

作者： Yufei Wang Juan Liu Xiaowei Ma xing-jie liang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 China University of Chinese Academy of Sciences Beijing 100049 China Tissue Engineering Lab Beijing Institute of Transfusion Medicine Beijing 100850 China

Globally, cancer is growing at an alarming pace, which calls for development of more efficient cancer treatments. Conventional chemotherapy and radiotherapy have become crucial first-line clinical treatments for cancer. However, along with their wide usage, limited therapeutic effects, severe adverse reactions, unaffordable costs, and complicated operations lead to failures of these treat- ments. Moreover, the emergence of multidrug resistance inhibits the longtirne usage of chemotherapeutics. One of the major causes of treatment failure is the insufficient sensitivity of cancer cells to therapeutic drugs or treatments. With the rigorous development of nanotechnolog~ tailored nanoparticles can efficiently sensitize malignant cells by inducing intracellular structural and functional changes, which could affect vital intracellular processes such as metabolism, signal conduction, proliferation, cell death as well as intracellular drug delivery. Here, we review recent advances in nanomaterial-assisted sensitization of oncotherapy, and challenges and strategies in the development of nanomedical approaches.

关键词： nanomaterial oncotherapy sensitization of oncotherapy mulfidrug resistance

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Nanobiotechnology and nanomedicine:small change brings big difference

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Science China(Life Sciences) 2018年第4期61卷 371-372页

作者： Shizhu Chen xing-jie liang CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology of China Beijing 100190 China College of Chemistry & Environmental Science Chemical Biology Key Laboratory of Hebei Province Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education Hebei University Baoding 071000 China University of Chinese Academy of Sciences Beijing 100049 China

The physicist Richard Feynman put forward the concept of nanotechnology in his famous speech, ＂There＇s Plenty of Room at the Bottom,＂ at the annual meeting of the American Physical Society on December 29, 1959. He began with a ＂bottom up＂ approach and proposed assembling from a single molecule or even an atom to meet the requirements of the design. He indicated that the laws of physics do not rule out the possibility of making an object by atom stack and predicted that our precise control over tiny objects could significantly expand the scope of material attributes acquired by human beings. Furthermore, in his report published in 1960, Richard Feynman proposed the concept of nanosur- gery and nanodrug delivery devices for the first time and further predicted that nanotechnology will play an important role in the field of life and health sciences in the future （Feynman, 1960）.

关键词：硬币物理学家纳米技术原子集合单个分子精确控制底部预言

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Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication

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Acta Pharmaceutica Sinica B 2020年第2期10卷 239-248页

作者： Chenyang Xiang Yuxuan Zhang Weisheng Guo xing-jie liang Translational Medicine Center Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences&the Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China

Nowadays,nanotechnology is revolutionizing the approaches to different fields from manufacture to *** nanotubes(CNTs)as promising candidates in nanomedicine have great potentials in developing novel entities for central nervous system pathologies,due to their excellent physicochemical properties and ability to interface with neurons and neuronal ***,most of the studies mainly focused on the drug delivery and bioimaging applications of CNTs,while neglect their application prospects as therapeutic drugs *** present,the relevant reviews are not available *** we summarized the latest advances on the biomedical and therapeutic applications of CNTs in vitro and in vivo for neurological diseases treatments as inherent therapeutic *** biological mechanisms of CNTs-mediated bio-medical effects and potential toxicity of CNTs were also intensely *** is expected that CNTs will exploit further neurological applications on disease therapy in the near future.

关键词： Carbon nanotubes Nervous system diseases Drug delivery Therapeutic drug Inherent medication Toxicity

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Intracellular aggregations of biological elements:From simple to complex

Aggregate

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Aggregate 2021年第3期2卷 14-20页

作者： Fangzhou Li Xinmiao Lan xing-jie liang 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 TechnologyBeijingChina Discipline of Oral and Maxillofacial Surgery Faculty of DentistryThe University of Hong KongHong Kong SARChina University of Chinese Academy of Sciences BeijingChina

Most cellular elements could be functioned by forming aggregate structures through interactions with other molecules,which is like the luminescence mechanism of AIE ***,in comparison to AIE molecules,the aggregation of biological elements appears to be more complex due to membership and mechanism,which is in line with the trend in biological evolution following the principle of simplicity to ***,we chose three distinctive examples because they differ significantly in their composition and show a progression from simple to complex,namely protein–protein complexes,protein–nucleic acid complexes,and protein–nucleic acid–lipid *** majority of units that perform functions within cells belong to these three *** discuss the formation mechanisms and related functions of the protein–protein complex(PML-NB),the proteins–nucleic acids complex ribosome,and the proteins–nucleic acids–lipids complex exosome,and hope to provide expert insight for related fields.

关键词： exosome PML nuclear body PML-NBs ribosome

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Reprogramming the tumor immune microenvironment via nanomaterial-mediated dynamic therapy

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Nano Research 2023年第12期16卷 13100-13112页

作者： Wangbo Jiao Yao Feng Chen liang Qiaoyi Lu Haiming Fan xing-jie liang Xiaoli Liu Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education College of Chemistry and Materials ScienceNorthwest UniversityXi’an 710069China 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 Institute of Regenerative and Reconstructive Medicine Med-X InstituteFirst Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710049China

Our improved knowledge of tumor immunology laid a solid foundation for the clinical use of tumor immunotherapies such as immune checkpoint blockers,and the efficacy of these drugs increased our confidence that immunomodulation was a viable way of treating *** basis of immunotherapy is to break the immune escape of the tumor and resolve the immune suppressive microenvironment of ***-mediated dynamic therapy(NDT)is an emerging immuno-regulatable type for tumor therapy,whose effects are mediated by increased cellular levels of reactive oxygen species(ROS).ROS is a potent trigger of immunogenic cell death,and this process initiates antitumor *** for use in NDT can be engineered to interact with almost all cell types in the tumor microenvironment to remodel this *** this review,we systematically examined the effects of NDT on four major cell types in the tumor microenvironment,namely tumor cells,lymphocytes,myeloid cells,and tumor stromal *** believe that this review will improve researchers’understanding of the anti-tumor immunity triggered by NDT,and provide ideas and inspiration for how optimally designed NDT schemes can be used to target the cells in the tumor microenvironment.

关键词： tumor immunotherapy tumor immune microenvironment nanomaterials reactive oxygen species immune cells

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A micelle-based stage-by-stage impelled system for efficient doxorubicin delivery

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Bioactive Materials 2023年第7期25卷 783-795页

作者： Sunfan Li Fangzhou Li Dong Wan Zuqin Chen jie Pan xing-jie liang School of Chemical Engineering and Technology Tiangong UniversityTianjin300387PR China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaNo.11First North RoadZhongguancunBeijing100190PR China University of Chinese Academy of Sciences Beijing100049PR China Medical School of Chinese PLA No.28 Fuxing RoadBeijing100853PR China Department of Radiology The First Medical CentreChinese PLA General HospitalBeijingPR China Department of Radiology Chinese PAP Guangxi Corps HospitalNanningGuangxiPR China

Chemotherapy remains the mainstay of cancer treatment,benefiting millions of patients each year,but the side effects of chemotherapy drugs severely limit their clinical ***(DOX)can cause various side effects such as heart damage and treatment-related *** effective use of active and passive targeting will improve the clinical application of ***,TPGS3350 and bioactive peptides were utilized to construct a micelle-based stage-by-stage impelled efficient system(missiles)for DOX delivery(DOX missiles).By taking advantage of the EPR effect,DOX missiles are efficiently enriched at the tumor *** being cleaved by matrix metalloproteinase2(MMP2),the peptide(VRGD)targets tumor cells to facilitate uptake of the missiles by the tumor cells via receptor-mediated *** intracellular activated caspase-3-catalyzed explosion of DOX missiles further enables efficient tumor *** study provides an efficient approach for DOX delivery and toxicity reduction.

关键词： Doxorubicin Delivery Peptide Missiles Chemotherapy

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Engineered nanoparticles circumvent the adaptive treatment tolerance to immune-checkpoint blockade therapy

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Science China Chemistry 2019年第12期62卷 1557-1560页

作者： Weisheng Guo Lu Liu Chenyang Xiang Jingqi Chen xing-jie liang Translational Medicine Center Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences&The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China

The fight against cancer has witnessed the rapid develop・ment of various therapeutic methodologies,including chemotherapy,surgery,radiotherapy,phototherapy,and the emerging immunotherapy[1].However,malignancies evolve adaptive tolerance under the threatening conditions upon therapies because of some potential biological or genetic mutations,which may cause serious adverse events,compromised therapeutic efficacy and even treatment *** instance,following the standard chemotherapy with paclitaxel,primary breast cancer can release exosomes that facilitate the seeding and growth of metastatic cancer cells in distant organs[2].Therefore,the term"adaptive treatment tolerance"(ATT),rather than"drug resistance",has been employed to better describe the dynamic evolution of this phenomenon during/post cancer therapy.

关键词： chemotherapy organs treatment

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