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Redox-responsive micelles integrating catalytic nanomedicine and selective chemotherapy for effective tumor treatment

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Chinese Chemical Letters 2021年第10期32卷 3076-3082页

作者： Ronghua Jin Zhongning Liu Tao Liu Pingyun Yuan Yongkang Bai Xin Chen School of Chemical Engineering and Technology Shaanxi Key Laboratory of Energy Chemical Process IntensificationInstitute of Polymer Science in Chemical EngineeringXi'an Jiao Tong UniversityXi’an 710049China Pharmaceutical College Guangxi Medical UniversityBeijing 100081China Department of Prosthodontics Peking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyNanning 530021China

Chemotherapy is one of the most conventional modalities for cancer ***,the high multidrug resistance of tumor cells still limited the clinical application of current *** the ability of nitric oxide(NO) to modulate potent P-glycoprotein to inhibit multi-drug resistance,a synergistic methodology combining chemotherapy and sustained NO generation is an ideal way to further promote the ***,a multi-functional micelle with tumor-selective chemotherapy driven by redox-triggered doxorubicin(DOX) release and drug resistance inhibition based on intracellular NO generation was fabricated for effective tumor *** micelle consists of DOX as core,arginine/glucose oxidase(Arg/GOx) as shell and redox-responsive disulfide bond as a linker,which is denoted as *** Arg serves as the biological precursor of nitric oxide for inhibition of multi-drug resistance to promote chemotherapy and GOx catalyzes glucose to produce hydrogen peroxide(H_(2) O_(2)) for increasing the generation of ***,the glucose supply could be simultaneously blocked by the catalytic process,which further enhanced therapeutic *** micelle requests a tumor-specific microenvironment(a considerable amount of GSH) to perform synergistic therapeutics including chemotherapy,starvation therapy(catalytic medicine),and gas therapy for tumor treatment,which resulted in significant cytotoxicity to tumor tissue.

关键词： Chemotherapy Gas therapy Starvation therapy Carrier-free tumor treatment

Exosomes-mediated tumor treatment: One body plays multiple roles

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Asian Journal of Pharmaceutical Sciences 2022年第3期17卷 385-400页

作者： Na Xu Ranran Guo Xiaotong Yang Ning Li Jia Yu Peng Zhang Shenyang Pharmaceutical University Shenyang 110016China

Exosomes are vesicles secreted by a variety of living cells,containing proteins,RNA and other components,which are nanoscale capsules commonly existed in the *** play important roles in a variety of physiological and pathological processes by participating in material and information exchange between cells,which can playmultiple roles in tumor *** the one hand,exosomes can be used as carriers and biomarkers,participate in the apoptosis signaling pathway and improve chemotherapy resistance,thus playing beneficial roles in tumor *** the other hand,exosomes play unfavorable roles in tumor *** cell exosomes contain PD-L1,which is a nuclear weapon for tumor growth,metastasis,and *** addition,exosomes can not only promote the epithelial-mesenchymal transition process,tumor angiogenesis and chemoresistance,but also participate in the autocrine *** this review,the multiple roles of exosomes and their prospects in the treatment of tumor were reviewed in detail.

关键词： Extracellular vesicles Exosomes Multiple roles tumor treatment

The role of tumor-associated macrophages(TAMs) in tumor progression and relevant advance in targeted therapy

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2156-2170页

作者： Qiyao Yang Ningning Guo Yi Zhou Jiejian Chen Qichun Wei Min Han Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China

Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to ***,monocytes and macrophages are recruited to the sites where the tumor *** the guidance of different microenvironmental signals,macrophages would polarize into two functional phenotypes,named as classically activated macrophages(M1)and alternatively activated macrophages(M2).Contrary to the anti-tumor effect of M1,M2 exerts anti-inflammatory and tumorigenic *** progressive tumor,M2 tumor-associated macrophages(TAMs)are in the majority,being vital regulators reacting upon *** review elaborates on the role of TAMs in tumor ***,prospective macrophage-focused therapeutic strategies,including drugs not only in clinical trials but also at primary research stages,are summarized followed by a discussion about their clinical application *** systems with efficient drug delivery and improved antitumor effect are also summed up in this article.

关键词： tumor-associated macrophages tumor microenvironment Targeted drug delivery tumor treatment Combined therapy Immunotherapy Extracellular vesicles Nano-drug

Metal-based inorganic nanocrystals for biological sonodynamic therapy applications:recent progress and perspectives

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Rare Metals 2024年第2期43卷 413-430页

作者： Dong Wang Jia-Tao Zhang Institute of Medical-Industrial Integration Beijing Key Laboratory of Structurally Controllable Advanced Functional Materials and Green ApplicationsSchool of Materials Science and EngineeringBeijing Institute of TechnologyBeijing100081China Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering Ministry of Industry and Information TechnologySchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing100081China

With the fast development of technology for the treatment of tumor and bacteria,photo-therapeutic strate-gies emerge as a kind of highly effective and common treatment,but the low tissue penetration depth of light limits their *** therapy(SDT),as an efficient and non-invasive treatment,attracts more people's attention due to the inherent property of high tissue *** soft tissue penetration depth of ultrasound(US)can even reach more than 10 cm,which has great advantage over that of ***,many sonosensitizers are studied and applied to SDT-based ***-based inorganic nanocrystals are able to generate more reactive oxygen species(ROS)due to the special composition and band *** representative achievements and the specific functions of the nanocrystals sonosensitizers are summarized in this work,and the relationship of structure/composition-SDT performance and the internally regulated composite is ***-gistic effects of SDT in combination with other therapeutic modalities are mainly *** the same time,the critical and potential issues and future perspectives are addressed.

关键词： Metal-based inorganic nanocrystals Sonodynamic therapy(SDT) tumor treatment Antibacteria

Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2110-2124页

作者： Jin Li Diane J.Burgess Department of Pharmaceutical Sciences University of ConnecticutStorrsCT 06269-3092USA

The complex tumor microenvironment is a most important factor in cancer *** biological microenvironment is composed of a variety of barriers including the extracellular matrix and associated cells such as endothelia cells,pericytes,and cancer-associated *** strategies can be utilized to enhance nanoparticle-based drug delivery and distribution into tumor tissues addressing the extracellular matrix or cellular *** addition to the biological microenvironment,the immunological conditions around the tumor tissue can be very complicated and cancer cells have various ways of evading immune *** drug delivery systems can enhance cancer immunotherapy by tuning the immunological response and memory of various immune cells such as T cells,B cells,macrophages,and dendritic *** this review,the main components in the tumor biological and immunological environment are *** focus is on recent advances in nanoparticle-based drug delivery systems towards targets within the tumor microenvironment to improve cancer chemotherapy and immunotherapy.

关键词： tumor microenvironment Nanoparticles Drug delivery tumor immunology tumor treatment tumor targeting Immunotherapy Combinational therapy

STAT3-specific nanocarrier for shRNA/drug dual delivery and tumor synergistic therapy

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Bioactive Materials 2024年第11期41卷 137-157页

作者： Le Sun Jishang Sun Cuiyao Li Keying Wu Zhiyang Gu Lan Guo Yi Zhou Baoqin Han Jing Chang College of Marine Life Science Ocean University of ChinaQingdao266003PR China Laboratory for Marine Drugs and Bioproducts Qingdao Marine Science and Technology CenterQingdao266237PR China

Non-small cell lung cancer(NSCLC)is a major disease with high incidence,low survival rate and prone to develop drug resistance to *** mechanism of secondary drug resistance in NSCLC chemotherapy is very complex,and studies have shown that the abnormal activation of STAT3(Signal Transducer and Activator of Transcription 3)plays an important role in *** this study,the pGPU6/GFP/Neo STAT3-shRNA recombinant plasmid was constructed with STAT3 as the precise *** modifying hydrophilic and hydrophobic blocks onto chitosan,a multifunctional vitamin E succinate-chitosan-polyethylene glycol monomethyl ether histidine(VES-CTS-mPEG-His)micelles were *** micelles could encapsulate hydrophobic drug doxorubicin through self-assembly,and load the recombinant pGPU6/GFP/Neo STAT3-shRNA(pDNA)through positive and negative charges to form dual-loaded nanoparticles DOX/VCPH/*** co-delivery and synergistic effect of DOX and pDNA could up-regulate the expression of PTEN(Phosphatase and Tensin Homolog),down-regulate the expression of CD31,and induce apoptosis of tumor *** results of precision targeted therapy showed that DOX/VCPH/pDNA could significantly down-regulate the expression level of STAT3 protein,further enhancing the efficacy of *** this study,precision personalized treatment of NSCLC could be effectively achieved,reversing its resistance to chemotherapy drugs,and providing new strategies for the treatment of drug-resistant NSCLC.

关键词： Synergistic therapy Short hairpin RNA STAT3 signaling pathway Drug delivery tumor treatment

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4327-4347页

作者： Yanyan Xu Jingyuan Xiong Xiyang Sun Huile Gao Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Healthy Food Evaluation Research Center West China School of Public Health and West China Fourth HospitalSichuan UniversityChengdu 610041China Hongqiao International Institute of Medicine Tongren HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200336China

Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies,on account of its good safety and long-term memory ***,low patient response rates and potential immune-related side effects make it rather challenging to literally bring immunotherapy from bench to ***,it has become evident that,although the immunosuppressive tumor microenvironment(TME)plays a pivotal role in facilitating tumor progression and metastasis,it also provides various potential targets for remodeling the immunosuppressive TME,which can consequently bolster the effectiveness of antitumor response and tumor ***,the particular characteristics of TME,in turn,can be exploited as avenues for designing diverse precise targeting *** general,it is of urgent necessity to deliver nanomedicines for remodeling the immunosuppressive TME,thus improving the therapeutic outcomes and clinical translation prospects of ***,we will illustrate several formation mechanisms of immunosuppressive *** importantly,a variety of strategies concerning remodeling immunosuppressive TME and strengthening patients'immune systems,will be ***,we will discuss the existing obstacles and future perspectives in the development of antitumor ***,the thriving bloom of immunotherapy will bring vibrancy to further exploration of comprehensive cancer treatment.

关键词： Cancer immunotherapy Immunosuppressive tumor microenvironment tumor microenvironment normalization Targeted nanomedicines Drug delivery Environment-responsive nanoparticles Combinational therapy tumor treatment

Progress in oncolytic viruses modified with nanomaterials for intravenous application

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Cancer Biology & Medicine 2023年第11期20卷 830-855页

作者： Liting Chen Zhijun Ma Chen Xu Youbang Xie Defang Ouyang Shuhui Song Xiao Zhao Funan Liu Department of Surgical Oncology and General Surgery Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsMinistry of EducationThe First Affiliated Hospital of China Medical UniversityShenyang 110001China Phase IClinical Trials Center Ministry of EducationThe First Affiliated Hospital of China Medical UniversityShenyang 110102China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBejing 100190China Department of General Surgery Panjin People's HospitalPanjin 124221China Department of Hematology and Rheumatology Qinghai Provincial People's HospitalXining 810007China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBejing 100049China IGDB-NCNST Joint Research Center Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

In oncolytic virus(OV)therapy,a critical component of tumor immunotherapy,viruses selectively infect,replicate within,and eventually destroy tumor ***,this therapy activates immune responses and mobilizes immune cells,thereby eliminating residual or distant cancer ***,because of OVs’high immunogenicity and immune clearance during circulation,their clinical applications are currently limited to intratumoral injections,and their use is severely *** recent years,numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous *** most commonly used nanomaterials for modifying OVs are liposomes,polymers,and albumin,because of their biosafety,practicability,and *** aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application.

关键词： Oncolytic virus nanomaterials drug delivery tumor treatment intravenous application

Lipid-conjugated siRNA hitchhikes endogenous albumin for tumor immunotherapy

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Chinese Chemical Letters 2023年第11期34卷 202-208页

作者： Bo Hu Sudong Kong Yuhua Weng Deyao Zhao Abid Hussain Qingze Jiao Shijing Zhan Ling Qiu Jianguo Lin Minhao Xie Bo Li Yuanyu Huang School of Life Science Advanced Research Institute of Multidisciplinary ScienceSchool of Medical TechnologyKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Key Laboratory for Separation and Analysis in Biomedicine and PharmaceuticalsBeijing Institute of TechnologyBeijing 100081China School of Chemical and Material Engineering Jiangnan UniversityWuxi 214122China NHC Key Laboratory of Nuclear Medicine Jiangsu Key Laboratory of Molecular Nuclear MedicineJiangsu Institute of Nuclear MedicineWuxi 214063China Department of Radiation Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China School of Materials and the Environment Beijing Institute of TechnologyZhuhai 519085China Rigerna Therapeutics Suzhou 215127China

With the development of a small interfering RNA(siRNA)delivery strategy,increasing siRNA therapeutics for tumor treatment appeared in clinical trials and pre-clinical ***,the test results of such therapeutics unveiled that efficient siRNA delivery to tumor tissues is still *** is considered an ideal carrier for delivering hydrophobic agents into tumor tissue because it is highly concentrated and long-circulating in blood and has propensity of tumor ***,we synthesized lipid conjugated siRNAs(LsiRNAs),which showed high affinity to ***,LsiRNAs non-covalently bind to the hydrophobic core of albumin through its octadecyl *** small size of albumin/LsiRNAs allows the complex to penetrate tumor tissue *** test proved that albumin extremely prolonged circulation time and increased tumor retention of associated ***,LsiRNA against programmed death ligand-1(Pdl1)efficiently suppressed tumor growth as well as prolonged survival time of tumor bearing mice by increasing infiltration of CD8^(+)T cells as well as promoted the maturation of dendritic cells both in tumor and ***,LsiRNAs provide a simple but effective way for siRNA tumor delivery that“hitchhikes”on albumin.

关键词： Albumin siRNA Lipid conjugate tumor treatment Immunotherapy