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Chinese Journal of Structural Chemistry 2020年第1期39卷 66-78,3页

作者： YING Jia-Wen SUN Qun YANG Li-Fang KE Mei-Rong HUANG Jian-Dong College of Chemistry State Key Laboratory of Photocatalysis on Energy and EnvironmentFujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and ChemotherapyFuzhou UniversityFuzhou 350116China

We design and synthesize a series of novel silicon(IV)phthalocyanines(SiPcs,1a,2a,1b,and 2b)axially conjugated with arginine or arginine-containing oligopeptides(Arg-Arg,Cys-Arg,Cys-Arg-Arg)through ester or ether linkers to demonstrate the effects of substituents and coupling ways on the spectral behaviors and photodynamic *** ester-linked SiPcs(1a and 2a)show slight red-shift,higher fluorescence emission and singlet oxygen generation compared to the ether-linked analogues(1b and 2b)due to the stronger electron-withdrawing ability of the ester group,suggesting that electronic effect of the linkers plays an important role in their spectral *** introduction of arginine could effectively reduce the aggregation of phthalocyanine in aqueous *** higher cellular uptake and plasma membrane localization ability,1b and 2b exhibit significantly higher photocytotoxicity against both HepG2 and Hela ***,the in vivo fluorescence imaging suggests that 2b is the most specific toward H22 tumor-bearing ICR mice,and it shows efficient tumor growth inhibition with the tumor inhibition rate up to 93%.Thus,this work would provide a new reference for the development of phthalocyanine-based photosensitizers.

关键词： photodynamic therapy phthalocyanine arginine spectral property anticancer activity

Nanostructured self-assemblies of photosensitive dyes: green and efficient theranostic approaches

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Green Chemical Engineering 2023年第4期4卷 399-416页

作者： Hao Liu Xue-Yan Li Xingshu Li Jian-Dong Huang College of Chemistry State Key Laboratory of Photocatalysis on Energy and EnvironmentFujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and ChemotherapyFuzhou UniversityFuzhou350108China

Recently,nano theranostics,by integrating diagnostic and therapeutic functions into a nano system,have provided increasing opportunities for the design of personalized medicine in *** the construction method of various theranostic nano systems,the design of single component nanoparticles which are composed of organic photosensitive dyes has become a promising approach to constructing multifunctional nano-theranostic systems,thanks to its unique advantages such as defined structure,100%loading,and high ***,depending on the inherent photonic imaging and therapeutic properties of the photosensitive dyes,the multifunctional purpose which integrates theranostic effects and targeting abilities can be realized via reasonable molecular modification and supramolecular *** this review,recent advances in the development of nanostructured self-assemblies of porphyrins,phthalocyanines,and boron-dipyrromethanes for theranostics are *** on their design consideration and theranostic applications are ***,prospects for clinical practice and potential challenges of this rapidly growing field are also provided.

关键词： Theranostic Dye Photosensitizer Multifunctional nanoparticle Self-assembly

A novel nanoparticle drug delivery system:tumor-exosome encapsulated DOX for breast cancer treatment and cancer metastasis chemoprevention

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中国药理学与毒理学杂志 2019年第10期 895-896页

作者： ZHOU Yu XIE Xiao-dong NIE Hui-fang JIA Lee Cancer Metastasis Alert and Prevention Center and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment College of ChemistryFujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy Fuzhou University Institute of Oceanography Minjiang University

OBJECTIVE To demonstrate the advantages of tumor exosomes as carriers for "natural nanoparticles" for drug delivery. METHODS The differences in various aspects of exosomes(such as particle size,potential, surface protein, etc.) before and after drug loading(DOX) were compared. Flow cytometry analysis and distribution of exosomes in mice verified the specificity of tumor exosomes for distal tissues, and additionally analyzed the natural targeting of tumor exosomes by confocal experiments and flow cytometry. Tumor exosomes surface protein knockout experiments demonstrate that exosomes indicate that proteins can increase drug delivery efficiency. Animal experiments verify that tumor exosomes loaded with drugs(DOX) inhibit tumor growth and tumor metastasis. RESULTS There were no significant differences in various aspects of exosomes(such as particle size, potential, surface protein, etc.) before and after drug loading(DOX). Confocal and flow analysis showed that the tumor exosomes had good targeting. CD47 knockout experiments demonstrate that tumor exosomes act as drug carriers to reduce the body′ s immune response and enhance drug targeting and delivery efficiency. CONCLUSION Tumor exosomes have great potential and advantages as a targeted drug carrier in the treatment of tumors and prevention of tumor metastasis.

关键词： exosome tumor metastasis drug deliver

Cancer metastasis chemoprevention prevents circulating tumour cells from germination

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4053-4068页

作者： Xiaodong Xie Yumei Li Shu Lian Yusheng Lu Lee Jia College of Materials and Chemical Engineering Minjiang UniversityFuzhouFujian350108China School of Basic Medicine Gannan Medical UniversityGanzhouJiangxi341000China Cancer Metastasis Alert and Prevention Center College of ChemistryFujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and ChemotherapyFuzhou UniversityFuzhouFujian350116China

The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into *** cancer crusade costs trillions with disappointing returns,teasing the possibility of a new *** for cancer post-metastases still seems tantalisingly out of *** metastasized,cancer-related death is extremely difficult,if not impossible,to be *** we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells(CTCs)from initiating metastases safely and effectively,and is disparate from the traditional cancer chemotherapy and cancer *** learning of the biology of CTCs and their disseminating organotropism,complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche(the first and the most important part in cancer metastatic cascade)can be pharmaceutically interrupted,the lethal metastatic cascade could be prevented from getting *** analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination,provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis *** adhesion/inhibition ratio(AIR)is defined for selecting the best cancer metastasis chemopreventive *** successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.

关键词： metastasis prevention reversed

A smart dual-drug nanosystem based on coassembly of plant and food-derived natural products for synergistic HCC immunotherapy

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Acta Pharmaceutica Sinica B 2021年第1期11卷 246-257页

作者： Bingchen Zhang Jiali Jiang Pengyu Wu Junjie Zou Jingqing Le Juanfang Lin Chao Li Bangyue Luo Yongjie Zhang Rui Huang Jingwei Shao Fujian Provincial Key laboratory of Cancer Metastasis chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhou 350116China Institute of Oceanography Minjiang UniversityFuzhou 350108China

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent ***,the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical ***,a novel"core-shell"co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid(UA)and polyphenol(EGCG)with the EpCAM-aptamer modification for hepatocellular carcinoma(HCC)synergistic *** the nature products derived from food-plant,UA and EGCG had good anticancer activities and low *** the simple and"green"method,the nanodrugs had the advantages of good stability,p H-responsive and strong penetration of tumor tissues,which was expected to increase tumor cellular uptake,long circulation and effectively avoid the potential defects of traditional *** nanocomplex exhibited the low cytotoxicity in the normal cells in vitro,good biosafety of organic tissues and efficient tumor accumulation in ***,UA combined with EGCG showed the immunotherapy by activating the innate immunity and acquired immunity resulting in significant synergistic therapeutic *** research could provide new ideas for the research and development of self-assembly delivery system in the future,and offer effective intervention strategies for clinical HCC treatment.

关键词： Natural product Ursolic acid EGCG Aptamer Co-assembly Nanodrug HCC Synergistic treatment Immunotherapy

Recent progress in sono-photodynamic cancer therapy:From developed new sensitizers to nanotechnology-based efficacy-enhancing strategies

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2197-2219页

作者： Yilin Zheng Jinxiang Ye Ziying Li Haijun Chen Yu Gao Cancer Metastasis Alert and Prevention Center College of ChemistryFuzhou UniversityFuzhou 350116China Fujian Provincial Key laboratory of Cancer Metastasis chemoprevention and Chemotherapy Fuzhou UniversityFuzhou 350116China

Many sensitizers have not only photodynamic effects,but also sonodynamic ***,the combination of sonodynamic therapy(SDT)and photodynamic therapy(PDT)using sensitizers for sonophotodynamic therapy(SPDT)provides alternative opportunities for clinical cancer *** significant advances have been made in synthesizing new sensitizers for SPDT,few of them are successfully applied in clinical *** anti-tumor effects of the sensitizers are restricted by the lack of tumor-targeting specificity,incapability in deep intratumoral delivery,and the deteriorating tumor *** application of nanotechnology-based drug delivery systems(NDDSs)can solve the above shortcomings,thereby improving the SPDT *** review summarizes various sensitizers as sono/photosensitizers that can be further used in SPDT,and describes different strategies for enhancing tumor treatment by NDDSs,such as overcoming biological barriers,improving tumor-targeted delivery and intratumoral delivery,providing stimuli-responsive controlled-release characteristics,stimulating anti-tumor immunity,increasing oxygen supply,employing different therapeutic modalities,and combining diagnosis and *** challenges and prospects for further development of intelligent sensitizers and translational NDDSs for SPDT are also discussed.

关键词： Sensitizers Sonodynamic therapy Photodynamic therapy Sono-photodynamic therapy Nanoparticles Drug delivery Cancer Efficacy-enhancing strategies

Pharmacometrics of nutraceutical sulforaphane and its implications in prostate cancer prevention

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Journal of Chinese Pharmaceutical Sciences 2016年第1期25卷 12-22页

作者： Sujit Nair Ah-Ng Tony Kong Amrita Cancer Discovery Biology laboratory Amrita Vishwa Vidyapeetham University Center for Cancer chemoprevention Research and Department of Pharmaceutics Rutgers The State University of New Jersey

Sulforaphane(SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapy regimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry. We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceutical SFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.

关键词： Pharmacometrics Pharmacokinetics Quantitative systems pharmacology Target engagement Metabolism Pharmacogenomics chemoprevention Sulforaphane Isothiocyanate Prostate cancer

Supramolecular phthalocyanine assemblies-enhanced synergistic photodynamic and photothermal therapy guided by photoacoustic imaging

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Aggregate 2024年第3期5卷 328-337页

作者： Yuan-Yuan Zhao Xiaojun Zhang Zixuan Chen Yihui Xu Heejeong Kim Hyunsun Jeong You Rim Lee Jiah Lee Xingshu Li Juyoung Yoon Fujian Provincial Key laboratory of Cancer Metastasis chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhouChina Department of Chemistry and Nanoscience Ewha Womans UniversitySeoulSouth Korea

Phototherapeutic nanoplatforms that combine photodynamic therapy(PDT)and photothermal therapy(PTT)with the guidance of photoacoustic(PA)imaging are an effective strategy for the treatment of tumors,but establishing a universal method for this strategy has been *** this study,we present a supramolecular assem-bly strategy based on Förster resonance energy transfer to construct a supramolecular nanostructured phototherapeutic agent(PcDA)via the anion and cation supramolec-ular interaction between two water-soluble phthalocyanine ramifications,PcD and *** approach promotes the absorption of energy,thus enhancing the genera-tion of reactive oxygen species(ROS)and heat by PcDA,improving its therapeutic efficacy,and overcoming the low photon utilization efficiency of conventional ***,after the intravenous injection of PcDA,neoplastic sites could be clearly visualized using PA imaging,with a PA signal-to-liver ratio as high as *** to these unique features,PcDA exhibits excellent antitumor efficacy in a preclinical model at a low dose of light *** study thus offers a general approach for the development of efficient phototherapeutic agents based on the simultaneous effect of PDT and PTT against tumors with the assistance of PA imaging.

关键词： Förster resonance energy transfer photoacoustic imaging photodynamic therapy photothermal therapy supramolecular assembly

Recent advances of sorafenib nanoformulations for cancer therapy:Smart nanosystem and combination therapy

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Asian Journal of Pharmaceutical Sciences 2021年第3期16卷 318-336页

作者： Fangmin Chen Yifan Fang Xiang Chen Rui Deng Yongjie Zhang Jingwei Shao Fujian Provincial Key laboratory of Cancer Metastasis chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhouFujian 350116China Institute of Oceanography Minjiang UniversityFuzhou 350108China

Sorafenib,a molecular targeted multi-kinase inhibitor,has received considerable interests in recent years due to its significant profiles of efficacy in cancer ***,poor pharmacokinetic properties such as limited water solubility,rapid elimination and metabolism lead to low bioavailability,restricting its further clinical *** the past decade,with substantial progress achieved in the development of nanotechnology,various types of smart sorafenib nanoformulations have been developed to improve the targetability as well as the bioavailability of *** this review,we summarize various aspects from the preparation and characterization to the evaluation of antitumor efficacy of numerous stimuli-responsive sorafenib nanodelivery systems,particularly with emphasis on their mechanism of drug release and tumor microenvironment *** addition,this review makes great effort to summarize the nanosystem-based combination therapy of sorafenib with other antitumor agents,which can provide detailed information for further synergistic cancer *** the final section of this review,we also provide a detailed discussion of future challenges and prospects of designing and developing ideal sorafenib nanoformulations for clinical cancer therapy.

关键词： Sorafenib Multi-kinase inhibitor Smart nanodelivery systems Tumor microenvironment Combination therapy

Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma

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Frontiers of Medicine 2023年第2期17卷 290-303页

作者： Yubing Zhou Xinyu He Yanan Jiang Zitong Wang Yin Yu Wenjie Wu Chenyang Zhang Jincheng Li Yaping Guo Xinhuan Chen Zhicai Liu Jimin Zhao Kangdong Liu Zigang Dong The Pathophysiology Department School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhou 450000China The China-US(Henan)Hormel Cancer Institute Zhengzhou 450000China State Key laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou 450000China Provincial Cooperative Innovation Center for Cancer chemoprevention Zhengzhou UniversityZhengzhou 450000China Cancer chemoprevention International Collaboration laboratory Zhengzhou 450000China Oncology Department The Tumor Hospital of Linzhou CityLinzhou 456500China

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.

关键词： benzydamine cyclin-dependent kinase 2 patient-derived xenograft esophageal squamous cell carcinoma