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In situ triggering antitumor efficacy of alcoholabuse drug disulfiram through Cu-based metalorganic framework nanoparticles

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Acta Pharmaceutica Sinica B 2021年第7期11卷 2016-2030页

作者： Lin Hou Yanlong Liu Wei Liu Mervat Balash Hongling Zhang Yi Zhang Huijuan Zhang Zhenzhong Zhang Biotherapy Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China School of Pharmacy School of Pharmaceutical SciencesZhengzhou UniversityKey Laboratory of Targeting Therapy and Diagnosis for Critical DiseasesZhengzhou 450001China

Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementation,and poor stability of DSF in vivo severely limited its application in cancer ***,we proposed an in situ DSF antitumor efficacy triggered system,taking advantages of Cu-based metal-organic framework(MOF).In detail,DSF was encapsulated into Cu-MOF nanoparticles(NPs)during its formation,and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and ***,DSF loaded Cu-MOF NPs maintained stability and integrity without Cu;leakage in blood circulation,thus showing excellent *** accumulating at tumor site,NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu;simultaneously in the hyaluronidase-enriched and acidic intracellular tumor *** profile lead to in situ chelation reaction between DSF and Cu;,generating toxic DSF/Cu complex against tumor *** in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs,which facilitated the tumor-specific chemotherapeutic effects of *** system provided a promising strategy for the application of DSF in tumor therapy.

关键词： Disulfiram Copper Metal-organic framework Hyaluronic acid Lysosomal escape DSF/Cu complex In situ antitumor therapy

Research Article Dynamically crosslinked nanocapsules for the efficient and serumresistant cytosolic protein delivery

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Nano Research 2024年第3期17卷 1760-1771页

作者： Qiang Yang Ningyu Liu Ziyin Zhao Xun Liu Lichen Yin Institute of Functional Nano and Soft Materials(FUNSOM) Jiangsu Key Laboratory of Carbon-Based Functional Materials and DevicesSoochow UniversitySuzhou 215123China Department of Thoracic Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China

Intracellular protein delivery is critical to the development of protein-based biopharmaceuticals and ***,current delivery vectors often suffer from complicated syntheses,low generality among various proteins,and insufficient serum ***,we developed an enlightened cytosolic protein delivery strategy by dynamically crosslinking epigallocatechin gallate(EGCG),low-molecular-weight polyethylenimine(PEI 1.8k),and 2-acetylphenylboric acid(2-APBA)on the protein surface,hence forming the EPP-protein nanocapsules(NCs).EGCG enhanced protein encapsulation via hydrogen bonding,and reduced the positive charge density of PEI to endow the NCs with high serum tolerance,thereby enabling effective cellular internalization in *** formation of reversible imine and boronate ester among 2-APBA,EGCG,and PEI 1.8k allowed acid-triggered dissociation of EPP-protein NCs in the endolysosomes,which triggered efficient intracellular release of the native *** strategy therefore showed high efficiency and universality for diversities of proteins with different molecular weights and isoelectric points,including enzyme,toxin,antibody,and CRISPR(clustered regularly interspaced short palindromic repeats)-Cas9 ribonucleoprotein(RNP),outperforming the commercial protein transduction reagent PULSin and RNP transfection reagent lipofectamine ***,intravenously(i.v.)injected EPP-saporin NCs efficiently delivered saporin into 4T1 tumor cells to provoke robust antitumor *** simple,versatile,and robust cytosolic protein delivery system holds translational potentials for the development of protein-based therapeutics.

关键词： nanocapsules dynamic crosslinking cytosolic protein delivery serum resistance antitumor therapy genome editing

Recent advances for liquid metals:Synthesis,modification and bio-applications

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Journal of Materials Science & Technology 2023年第12期143卷 153-168页

作者： Zhenhu Guo Xiaohan Gao Jingsong Lu Wanling Xu Jielin Ye Ying Li Wensheng Xie Lingyun Zhao Key Laboratory of Advanced Materials Ministry of Education of ChinaSchool of Materials Science and EngineeringTsinghua UniversityBeijing 100084China State Key Laboratory of New Ceramics and Fine Processing School of Materials Science and EngineeringTsinghua UniversityBeijing 100084China School of Medicine Tsinghua UniversityBeijing 100084China Department of Neurosurgery Yuquan HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 100084China The Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology(Ministry of Education) Department of ChemistryTsinghua UniversityBeijing 100084China

Considering the application requirements for modern biomedicine,research into novel biomaterials with unusual functions is highly *** an alternative,liquid metals(LMs),a nontraditional family of metal materials,have piqued the interest of biomedical researchers and made significant advances in biomed-ical areas,owing to their shape transformability,self-healing capability,excellent electrical,and thermal *** particular,many functionalized strategies for the preparation and modification of LMs or LMs-based composites to achieve extended biomedical applications have been investigated in recent *** findings provided inspiring while constructive reference for the fabrication and engineering of novel LMs-based ***,in this topic review,we elaborate on the recent advances of LMs-based functional materials,with particular focuses on the synthesis,modification,and bio-applications,especially in antitumor therapy,antibacterial,contrast agent for imaging,bone repair,electronic skin sen-sor,and nerve connection *** on,the current challenges and future prospects of LMs-based composites are carefully discussed.

关键词： Liquid metals Synthesis Composites antitumor therapy Bio-application

The TLR7 agonists imiquimod and gardiquimod improve DC-based immunotherapy for melanoma in mice

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Cellular & Molecular Immunology 2010年第5期7卷 381-388页

作者： Fang Ma Jianhua Zhang Jian Zhang Cai Zhang Institute of Immunopharmacology and Immunotherapy School of Pharmaceutical SciencesShandong UniversityJinanChina

Toll-like receptors(TLRs)are a family of highly conserved germline-encoded pattern-recognition receptors that are essential for host immune *** ligands represent a promising class of immunotherapeutics or vaccine adjuvants with the potential to generate an effective antitumor immune *** TLR7/8 agonists have aroused interest because they not only activate antigen-presenting cells but also promote activation of T and natural killer(NK)***,the exact mechanism by which stimulation of these TLRs promotes immune responses remains unclear,and different TLR7/8 agonists have been found to induce different *** this study,we demonstrate that both gardiquimod and imiquimod promote the proliferation of murine splenocytes,stimulate the activation of splenic T,NK and natural killer T(NKT)cells,increase the cytolytic activity of splenocytes against B16 and MCA-38 tumor cell lines,and enhance the expression of costimulatory molecules and IL-12 by macrophages and bone marrow-derived dendritic cells(DCs).In a murine model,both agonists improved the antitumor effects of tumor lysate-loaded DCs,resulting in delayed growth of subcutaneous B16 melanoma tumors and suppression of pulmonary ***,we found that gardiquimod demonstrated more potent antitumor activity than *** results suggest that TLR7/8 agonists may serve as potent innate and adaptive immune response modifiers in tumor *** importantly,they can be used as vaccine adjuvants to potentiate the efficiency of DC-based tumor immunotherapy.

关键词： antitumor therapy DC vaccine melanoma TLR TLR7/8 agonist

Super-sensitive bifunctional nanoprobe: Self-assembly of peptide-driven nanoparticles demonstrating tumor fluorescence imaging and therapy

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1473-1486页

作者： Han Xiao Rui Zhang Xiaobo Fan Xinglu Jiang Mingyuan Zou Xuejiao Yan Haiping Hao Guoqiu Wu Medical School Southeast UniversityNanjing 210009China Department of Clinical Laboratory the Fifth Affiliated Hospital of Sun Yat-sen UniversityNanjing 210009China Department of Cardiology the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical UniversityNanjing 210009China State Key Laboratory of Natural Medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityZhuhai 519000China Center of Clinical Laboratory Medicine Zhongda HospitalSoutheast UniversityNanjing 21009China Jiangsu Provincial Key Laboratory of Critical Care Medicine Southeast UniversityChangzhou 213000China

The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment;however,biocompatibility and targeted penetration of these nanomaterials remain as limitations,which lead to serious side effects and significantly narrow the scope of their *** self-assembly of intermediate filaments with arginine-glycine-aspartate(RGD)peptide(RGDIFP)was triggered by the hydrophobic cationic molecule 7-amino actinomycin D(7-AAD)to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor *** designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step *** fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes,ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted *** is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential,but also potent antitumor therapeutic effects in *** proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.

关键词： Nanoprobe 7-Amino actinomycin D Intermediate filament protein Tumor image antitumor therapy Integrin avβ3

Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2738-2748页

作者： Kailin Li Jieqiong You Qian Wu Wen Meng Qiaojun He Bo Yang Chengliang Zhu Ji Cao College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310058China Affiliated Hangzhou First People’s Hospital Zhejiang University School of MedicineHangzhou 310058China Cancer Center of Zhejiang University Hangzhou 310058China

Synthetic lethality is a proven effective antitumor strategy that has attracted great ***-scale screening has revealed many synthetic lethal genetic phenotypes,and relevant smallmolecule drugs have also been implemented in clinical *** evidence suggests that CDKs,constituting a kinase family predominantly involved in cell cycle control,are synthetic lethal factors when combined with certain oncogenes,such as MFC,TP53,and RAS,which facilitate numerous antitumor treatment options based on CDK-related synthetic *** this review,we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future.

关键词： Synthetic lethality Cyclin-dependent kinase antitumor therapy Oncogenes MYC P53 RAS PARP

Research advances of tetrahedral framework nucleic acid-based systems in biomedicine

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Chinese Chemical Letters 2024年第11期35卷 35-43页

作者： Lihang Wang Mary Li Javier Chunshan Luo Tingsheng Lu Shudan Yao Bing Qiu Yun Wang Yunfeng Lin Department of Spine Surgery Beijing Jishuitan Hospital Guizhou HospitalGuiyang 550014China State Key Laboratory of Oral Diseases National Center for StomatologyNational Clinical Research Centre for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Sichuan Provincial Engineering Research Center of Oral Biomaterials Chengdu 610041China

This article reviews the latest research advances of tetrahedral framework nucleic acid(t FNA)-based systems in their fabrication,modification,and the potential applications in *** arises from the synthesis of four single-stranded DNA *** chain contains brief sequences that complement those found in the other three,culminating in the creation of a pyramid-shaped nanostructure of approximately 10 nanometers in *** first generation of t FNA demonstrates inherent compatibility with biological systems and the ability to permeate cell membrane *** attributes translate into remarkable capabilities for regulating various cellular biological processes,fostering tissue regeneration,and modulating immune *** subsequent evolution of t FNA introduces enhanced adaptability and a relatively higher degree of biological *** advancement encompasses structural modifications,such as the addition of functional domains at the vertices or side arms,integration of low molecular weight pharmaceuticals,and the implementation of diverse strategies aimed at reversing multi-drug resistance in tumor cells or *** augmentations empower t FNA-based systems to be utilized in different scenarios,thus broadening their potential applications in various biomedical fields.

关键词： DNA nanomaterials Tetrahedral framework nucleic acid Drug delivery Antioxidation Immunomodulation Tissue regeneration antitumor therapy

Regulating Signal Pathway Triggers Circular Reactive Oxygen Species Production to Augment Oxidative Stress with Enzyme-Activated Nanoparticles

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CCS Chemistry 2024年第3期6卷 693-708页

作者： Benkai Bao Qiong Yuan Qian Feng Ling Li Meiqi Li Yanli Tang Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province Key Laboratory of Applied Surface and Colloid ChemistryMinistry of EducationSchool of Chemistry and Chemical EngineeringShaanxi Normal UniversityXi’anShaanxi Province 710119

Regulating antioxidative stress pathways to augment oxidative stress and enhance antitumor therapy is highly desirable but very ***,we initiated a multifunctional nanoparticle to regulate the Keap1-Nrf2 antioxidative stress pathway to promote cancer cell *** OPFV-SnMP@GE11 nanoparticles were assembled by enzyme-activated OPFV-TLQ,tin mesoporphyrin(SnMP),and ***-SnMP@GE11 accumulated at tumor sites through specific targeting with ***-TLQ was specifically reduced to a photosensitizer OPFVNH2 by endocellular NAD(P)H:quinone oxidoreductase 1(NQO1).Under irradiation,OPFV-NH2 greatly produced reactive oxygen species(ROS)through a type I mechanism,which activated the Keap1-Nrf2 signal pathway and enhanced the transcription of NQO1,resulting in a continuous and explosive generation of ***,SnMP inhibited the activity of heme oxygenase-1(HO-1),further depressing antioxidative *** strategy provides insight into the regulation of the signal pathway to amplify oxidative stress,paving the way to studying the molecular mechanisms of cellular activities to enhance cancer therapy.

关键词： Keap1-Nrf2 pathway enzyme-activated probe reactive oxygen species oxidative stress antitumor therapy

Preparation of NIR-II-excited Drug-loaded Liposomes and Their antitumor Activity and in Vitro Imaging Studies

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Advances in Modern Oncology Research 2019年第1期5卷 18-23页

作者： Nityi Nanda Lan Yang General Medicine Global College of Medical Sciences&Research and HospitalGarawa110034India China International Pharmaceutical Research Institute Beijing100000China

In recent years,with the rapid development of nano-technology,the combination of diagnosis and treatment by nanotechnologyhas brought new hope for mankind to overcome *** Near-infrared two-region(NIR-II)imaging technology hasdeveloped rapidly in recent years because of its non-invasive nature,strong tissue penetration and overall imaging of small *** this study,a novel nano-drug delivery system(DOX-IR1061 cationic liposomes)was prepared,loaded with doxorubicin(DOX)as a chemotherapeutic drug and NIR-II-excited fluorescent probe IR1061 as an imaging agent,and the uptake ability of tumor cellswas enhanced by ***-IR1061 cationic liposomes have good NIR-II imaging ability,clear imaging and *** uptake indicated that palamine could enhance the uptake efficiency of cationic liposomes by tumor cells,while in vitroanti-tumor experiments revealed that the enhancement of uptake efficiency would enhance the anti-tumor effect of ***,DOX-IR1061 cationic liposomes we prepared have the potential to realize both tumor imaging and therapy,and to realize theintegration of rapid diagnosis and treatment,and provide new ideas for cancer cure and the development of the field of diagnosis andtreatment integration.

关键词： NIR-II imaging Diagnosis and treatment integration antitumor therapy