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Designed fabrication of mesoporous silica-templated self-assembled theranostic nanomedicines

Science China Chemistry 2021年第2期64卷 204-217页

作者： fangyuan li&daishun ling Yang Du Zheng Chen Ji Young Lee Peihua lin Fan Xia Yunan Guan fangyuan li daishun ling Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of Biomedical Engineering of the Ministry of Education College of Biomedical Engineering&Instrument ScienceZhejiang UniversityHangzhou 310027China Hangzhou Institute of Innovative Medicine College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province Hangzhou 310009China

Theranostic nanosystems that integrate diagnosis and therapy have garnered increasing attention for personalized *** integration of the versatile nanoparticles to fabricate self-assembled theranostic nanomedicines becomes increasingly important in current medical *** silica nanoparticles(MSN)with their highly attractive physicochemical properties and favorable morphological attributes represent ideal templates for the controlled assembly and integration of functional nanomaterials to fabricate self-assembled theranostic *** rationally designed combination strategy and heterostructure will improve the overall bioavailability and preserve the unique property of each *** this review,the cutting-edge strategies for the designed fabrication of MSN-templated self-assembled nanomedicines are *** categorize MSN-based nanomedicines by their unique heterostructures,including core-shell,yolk-shell,core-satellite,heterodimer and core-shell-satellite structures,and discuss the controlled assembly approaches as well as the intriguing applications for disease ***,a perspective on the challenges in the clinical translation of self-assembled theranostic nanomedicines is highlighted.

关键词： self-assembly theranostics heterostructure mesoporous silica nanomedicines

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Metal nanoparticles for cancer therapy:Precision targeting of DNA damage

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1132-1149页

作者： Qian Chen Chunyan Fang Fan Xia Qiyue Wang fangyuan li daishun ling Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China World Laureates Association(WLA)Laboratories Shanghai 201203China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province Hangzhou 310009China

Cancer,a complex and heterogeneous disease,arises from genomic ***,DNA damage-based cancer treatments,including radiotherapy and chemotherapy,are employed in clinical ***,the efficacy and safety of these therapies are constrained by various factors,limiting their ability to meet current clinical *** nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer *** customizable physicochemical properties enable the development of targeted and personalized treatment *** this review,we delve into the design principles and optimization strategies of metal *** shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal *** encompass targeted drug delivery,inhibition of DNA repair mechanisms,induction of cell death,and the cascading immune ***,we explore the pivotal role of physicochemical factors such as nanoparticle size,stimuli-responsiveness,and surface modification in shaping metal nanoparticle ***,we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy,paving the way for novel treatment paradigms.

关键词： DNA damage Metal nanoparticles Nucleus-targeting DNA repair inhibition Immune response Size optimization Stimuli-responsiveness Surface modification

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Nature-inspired supramolecular assemblies for precise biomedical imaging and therapy

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Acta Pharmaceutica Sinica B 2022年第10期12卷 4008-4010页

作者： Yamin liu Qiyue Wang fangyuan li daishun ling Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China Department of Chemistry Shanghai Key Laboratory of Molecular Catalysis and Innovative MaterialsFudan UniversityShanghai 200438China Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China

To the editor:The precise diagnosis and effective therapy of refractory diseases,such as neurodegenerative diseases,coronary heart diseases and cancers,is critical to increase the survival rate and improve the life quality of *** of the conventional small molecular medicines are heavily associated with the limitations of poor solubility,low targeting efficiency,inducing drug resistance and systemic toxicity,promoting scientists to develop new strategies for overcoming these limitations.

关键词： Supramolecular assembly Biomedical applications Diagnosis Therapy Nature-inspired

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Tumor-responsive dynamic nanoassemblies for boosted photoimmunotherapy

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Nano Research 2023年第8期16卷 11125-11138页

作者： Dao Shi Nan Wang Jie Zhang Xi Hu Qiyue Wang Ruixue Xiao Baoyue Ding fangyuan li daishun ling Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational MedicineState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong UniversityShanghai 200240China Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Pharmaceutics Jiaxing Key Laboratory for Photonanomedicine and Experimental TherapeuticsCollege of MedicineJiaxing UniversityJiaxing 314001China World Laureates Association(WLA)Laboratories Shanghai 201203China School of Pharmacy Anhui University of Chinese MedicineHefei 230012China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province Hangzhou 310009China

Photoimmunotherapy(PIT)is an emerging therapeutic approach that integrates phototherapy and immunotherapy to eliminate primary tumors under an appropriate dosage of local light irradiation,while simultaneously preventing tumor metastasis and recurrence by activating the host antitumor immune ***-responsive dynamic nanoassemblies(TDNs)have evolved from being a mere curiosity to a promising platform for high-performance ***,the dynamic nano-bio interaction between TDNs and tumor microenvironment remains poorly understood,which shall be critical for precise control of TDNs assembling/disassembling behavior and superior PIT *** deepen the understanding of the structure–function relationship of TDNs,this review introduces the rational design,nano-bio interactions,and controllable functionalities of cutting-edge TDNs for enhanced ***,the synergetic mechanism between TDNs-based PIT and immunomodulatory agents-mediated immunomodulation is particularly ***,the challenges and future perspectives in this emerging field are assessed.

关键词： photoimmunotherapy tumor-responsive dynamic nanoassemblies immunosuppressive tumor microenvironment

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A K~+-sensitive AND-gate dual-mode probe for simultaneous tumor imaging and malignancy identification

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National Science Review 2022年第7期9卷 127-136页

作者： Qiyue Wang fangyuan li Zeyu liang Hongwei liao Bo Zhang Peihua lin Xun liu Shen Hu Jiyoung Lee daishun ling Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical Sciences Zhejiang University World Laureates Association (WLA) Laboratories Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational Medicine Shanghai Jiao Tong University Department of Obstetrics The Second Affiliated Hospital of Zhejiang University School of Medicine

Although molecular imaging probes have the potential to non-invasively diagnose a tumor,imaging probes that can detect a tumor and simultaneously identify tumor malignancy remain ***,we demonstrate a potassium ion(K+) sensitive dual-mode nanoprobe(KDMN) for non-invasive tumor imaging and malignancy identification,which operates via a cascaded ’AND’ logic gate controlled by inputs of magnetic resonance imaging(MRI) and fluorescence imaging(FI) *** encapsulate commercial K~+ indicators into the hollow cavities of magnetic mesoporous silica nanoparticles,which are subsequently coated with a K+-selective membrane that exclusively permits the passage of K+while excluding other *** KDMN can readily accumulate in tumors and enhance the MRI contrast after systemic *** information of the tumor lesion is thus accessible via MRI and forms the first layer of the ’AND’ ***,the KDMN selectively captures K+and prevents interference from other cations,triggering a K~+-activated FI signal as the second layer of the ’AND’ gate in the case of a malignant tumor with a high extracellular K~+*** dual-mode imaging approach effectively eliminates false positive or negative diagnostic results and allows for non-invasive imaging of tumor malignancy with high sensitivity and accuracy.

关键词： dual-mode imaging probe fluorescence imaging MRI tumor malignancy identification potassium ion

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A Sub-Nanostructural Transformable Nanozyme for Tumor Photocatalytic Therapy

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Nano-Micro Letters 2022年第6期14卷 282-293页

作者： Xi Hu Nan Wang Xia Guo Zeyu liang Heng Sun Hongwei liao Fan Xia Yunan Guan Jiyoung Lee daishun ling fangyuan li Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058People’s Republic of China Frontiers Science Center for Transformative Molecules State Key Laboratory of Oncogenes and Related GenesSchool of Chemistry and Chemical EngineeringNational Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Department of Clinical Pharmacy The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003People’s Republic of China WLA Laboratories Shanghai 201203People’s Republic of China Department of Biomedical-Chemical Engineering The Catholic University of Korea43 Jibong-roWonmi-guBucheon-SiGyeonggi-do 14662Republic of Korea

The structural change-mediated catalytic activity regulation plays a significant role in the biological functions of natural ***,there is virtually no artificial nanozyme reported that can achieve natural enzyme-like stringent spatiotemporal structure-based catalytic activity ***,we report a subnanostructural transformable gold@ceria(STGC-PEG)nanozyme that performs tunable catalytic activities via near-infrared(NIR)light-mediated sub-nanostructural *** gold core in STGC-PEG can generate energetic hot electrons upon NIR irradiation,wherein an internal sub-nanostructural transformation is initiated by the conversion between CeO;and electron-rich state of CeO;-x,and active oxygen vacancies generation via the hot-electron ***,the sub-nanostructural transformation of STGC-PEG enhances peroxidase-like activity and unprecedentedly activates plasmon-promoted oxidase-like activity,allowing highly efficient low-power NIR light(50 m W cm;)-activated photocatalytic therapy of *** atomic-level design and fabrication provide a platform to precisely regulate the catalytic activities of nanozymes via a light-mediated sub-nanostructural transformation,approaching natural enzyme-like activity control in complex living systems.

关键词： Nanozymes Sub-nanostructural transformation Catalytic activity Reactive oxygen species Photocatalytic therapy

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Platinum drugs:from Pt(Ⅱ)compounds,Pt(Ⅳ)prodrugs,to Pt nanocrystals/nanoclusters

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Science Bulletin 2017年第8期62卷 589-596页

作者： Xi Hu fangyuan li Nabila Noor daishun ling Zhejiang Province Key Laboratory of Anti-Cancer Drug Research College of Pharrnaceutical SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of Biomedical Engineering of the Ministry of Education College of Biomedical Engineering&Instrument ScienceZhejiang UniversityHangzhou 310027China

Platinum(Pt) based drugs, such as cisplatin, are widely used as anti-cancer agents, but their severe adverse reactions and resistance of cancer patients have limited their board clinical use. For the last few decades, Pt(Ⅱ) compounds, Pt(Ⅳ) prodrugs as well as smart drug delivery systems have been developed to overcome these problems. However, most conventional strategies rely on the similar anti-cancer mechanism with cisplatin and consequently only achieve limited success. Recently, Pt nanocrystals/nanoclusters(Pt NCs), with a brand new anti-cancer mechanism, have shown a promising potential in targeted cancer therapy, especially in Pt resistance circumvention. This review is helpful to understand the research strategies of Pt drugs, particularly, the recent developments and medical applications of Pt NCs.

关键词： Platinum Pt(Ⅱ) Pt(Ⅳ) Pt nanocrystals/nanoclusters Pt resistance Cancer therapy

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A mini-review and perspective on ferroptosis-inducing strategies in cancer therapy

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Chinese Chemical Letters 2019年第4期30卷 847-852页

作者： Shuaifei Wang Hongwei liao fangyuan li daishun ling Institute of Pharmaceutics College of Pharmaceutical Sciences Zhejiang University Hangzhou Institute of Innovative Medicine College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Biomedical Engineering of the Ministry of Education College of Biomedical Engineering & Instrument Science Zhejiang University

Ferroptosis, as a new type of cell death caused by lipid peroxidation, has attracted much attention since it was first identified in 2012. A lot of progress has been made in unraveling its mechanisms and therapeutic potential as a target for cancer therapy. Hitherto, there are mainly two strategies widely adopted for designing ferroptosis-inducing agents, which include increasing the intracellular reactive oxygen species(ROS) level by Fenton reaction, and inactivating the glutathione peroxidase 4(GPX4). In this mini-review,we summarize the recent advances in ferroptosis-based anticancer treatments with a highlight on nanomaterials, and discuss the current challenges faced by those agents from the perspective of in vivo applications. Moreover, by generalizing ferroptosis induced by excess iron ions to cell death caused by the polyvalent metal-mediated oxidative burden, we introduce a new paradigm of cancer treatment by exploiting various polyvalent metals to disrupt the vulnerable redox balance in cancer cells, which may greatly diversify our arsenal to combat cancer.

关键词： Ferroptosis Fenton reaction Reactive oxygen species lipid peroxidation Glutathione peroxidase 4

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不同频率下全身振动疗法对不随意运动型脑瘫患儿下肢粗大运动及步行功能的影响

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实用医学杂志 2024年第3期40卷 353-359页

作者：张秋虞记华李卫平凌运其王剑雄胥方元西南医科大学附属医院康复医学科西南医科大学康复医学系康复医学与工程泸州市重点实验室四川泸州646000

目的基于不同频率下全身振动疗法(whole body vibration,WBV)对不随意运动型脑瘫粗大运动及步行功能的影响,为后续WBV临床推广提供参考意义。方法选取2021年10月至2022年11月在西南医科大学附属医院康复医学科门诊和/或入院6~12岁不随... 详细信息

目的基于不同频率下全身振动疗法(whole body vibration,WBV)对不随意运动型脑瘫粗大运动及步行功能的影响,为后续WBV临床推广提供参考意义。方法选取2021年10月至2022年11月在西南医科大学附属医院康复医学科门诊和/或入院6~12岁不随意运动型脑瘫60例,按随机数字表法分为对照组(n=20)、(25±5)Hz组(n=20)及(35±5)Hz组(n=20)。3组均进行常规康复训练,(25±5)Hz组额外接受振动频率为(25±5)Hz的WBV,(35±5)Hz组接受(35±5)Hz的WBV,3组均治疗8周。在治疗前后对3组患儿使用Berg平衡量表(Berg Balance Scale,BBS)、起立-行走计时测试(Time to Up and Go Test,TUGT)、粗大运动功能测试量表(Gross Motor Function Measure-88,GMFM-88)及足印分析法评定疗效。结果治疗后3组患儿各项评分指标均优于治疗前(P<0.001);其中(35±5)Hz组BBS评分(F=12.502)、TUGT(F=8.211)、GMFM-88的D区、E区评分(F=12.802、8.505)、跨步长(F=12.279)、步宽(F=13.582)及1 min步行距离(F=12.619)均优于(25±5)Hz组及对照组(P<0.05或P<0.01);(25±5)Hz组疗效优于对照组(P<0.05或P<0.01)。结论WBV可提高不随意运动型脑瘫儿童躯干控制、改善其下肢粗大运动及步行功能,且(35±5)Hz的WBV疗效优于(25±5)Hz的WBV。

关键词：不同频率全身振动疗法不随意运动型脑瘫粗大运动步行功能

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Dynamic supraparticles for the treatment of age-related diseases

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Science Bulletin 2019年第24期64卷 1850-1874页

作者： Hongwei liao Zeyu liang Nan Wang Min Wei Ying Chen fangyuan li daishun ling Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Key Laboratory of Biomedical Engineering of the Ministry of Education College of Biomedical Engineering and Instrument ScienceZhejiang UniversityHangzhou 310058China

Age-related diseases(ARDs) are arising as a major threat to public health in our fast-aging *** development of nanomedicine has sparked much optimism toward ARDs management by improving drug delivery and controlled drug release. However, effective treatments for ARDs, such as cancer and Alzheimer’s diseases(AD), are still lacking, due to the complicated pathological features of ARDs including multifactorial pathogenesis, intricate disease microenvironment, and dynamic symptom manifestation. Recently, dynamic supraparticles(DS), which are reversibly self-assembled functional nanoparticles, have provided a novel strategy for combating ARDs. Besides the intrinsic advantages of nanomedicine including multifunctional and multitarget, DS are capable of dynamic structural reconfiguration upon certain stimulation, creating another layer of maneuverability that allows programmed response to the spatiotemporal alterations of ARDs during progression and treatment. In this review,we will overview the challenges faced by ARDs management, and discuss the unique opportunities brought by DS. Then, we will summarize the designed synthesis of DS for ARDs treatment. Finally, we will dissect the therapeutic targets in ARDs that can be exploited by DS, and present the encouraging advances in this field. Hopefully, this review will bridge our knowledge of the design principle of DS and ARDs management, which may inspire the future development of potent theranostic agents to improve the healthcare.

关键词： Dynamic supraparticles Age-related diseases Nanomedicine Stimuli-responsive

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