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Perylenediimide chromophore as an efficient photothermal agent for cancer therapy

Science Bulletin 2018年第2期63卷 101-107页

作者： Shaobo Zhang Jianhao Li Jie Wei meizhen yin State Key Laboratory of Chemical Resource Engineering Beijing Laboratory of Biomedical Materials Beijing University of Chemical Technology

Photothermal agents with improved bioavailabilities can generate heat from near-infrared light, which has been efficiently used for in vivo photothermal therapy （PTT） for cancer, with minimum tissue invasion. Strategies for developing organic near-infrared-absorbing molecules for phototfiermal cancer therapy have drawn intensive attention among academic investigators. However, conventional organic nearinfrared-absorbing molecules may not only have complex synthesis procedures, but also easily suffer from photobleaching under light irradiation. These drawbacks might lead to an increase in the synthesis cost, and elicit a risk of side effects in PTF. Thus, it is essential to devise an organic photothermal agent with stable phototbermal capacity, which involves a facile synthesis process. In this study, incorporating a secondary amine group （donor） in the bay regions of perylenediimides （PDls） could lead to a 150-nm bathochromic shift of the absorption maximum. Next, a modification of poly（ethylene glycol）（PEG） at the periphery of the chromophore renders the targeted macromolecule PDI-PEG highly water-soluble, and capable of intense absorption in the near-infrared region. The self-assembled PDl-based nanoparti- des （PDI-NPs） have a size of 55 nm in aqueous solutions. PDI-NPs with excellent photostability possess a high photothermal conversion efficiency of up to 43% ± 2%. Finally, PDI-NPs allow for efficient in vitro and in vivo photothermal cancer therapy. Meanwhile, PDI-NPs exhibit quite low cytotoxicity and no biotoxicity on major organs in vivo. Thus, these easily-manufactured PDI-NPs can serve as extremely stable photothermal agents for efficient photothermal cancer therapy.

关键词： Perylenediimides Photothermal therapy Photostability Biotoxicity

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A New Type of Nanogel Carrier based on Mixed Pluronic Loaded with Low-Dose Antitumor Drugs

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Journal of Wuhan University of Technology(Materials Science) 2019年第4期34卷 960-967页

作者： yin meizhen YU Xin School of Medicine Hubei Polytechnic UniversityHuangshi 435003China School of Medicine Inner Mongolia University for NationalitiesInner Mongolia Tongliao 028000China State Key Laboratory of Advanced Technology for Materials Synthesis and Processing and Biomedical Materials and Engineering CenterWuhan University of TechnologyWuhan 430070China

To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic■ F-127, which binds folic acid(FA), Pluronic■ F-68 and triptolide(TPL)(FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer(FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy(AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant(MDR) breast cancer cells(MCF-7/ADR cells) and induce cell death. The effects were significantly different from those of free TPL(P < 0.01). Using the fluorescent probe Nile red(Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FAF-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma(HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr(P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property,targeted tumor cells, a

关键词： pluronic nanogels nanodrug carriers triptolide

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Modulating planarity of cyanine dye to construct highly stable Haggregates for enhanced photothermal therapy

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Nano Research 2023年第1期16卷 970-979页

作者： Kai Wei Yanxin Wu Pengyu Li Xian Zheng Chendong Ji meizhen yin State Key Laboratory of Chemical Resource Engineering Beijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing 100029China

Self-assembly of dyes has become a flexible strategy to modulate their photophysical properties.H-aggregates show great potential to increase heat generation,while the precise designing of H-aggregates as efficient photothermal agents is still ***,a quinoline cyanine(QCy)is developed for constructing stable H-aggregated nanoparticles(NPs)to significantly enhance photostability and photothermal conversion efficiency(PCE).With symmetrical rigid planar quinoline structures,QCy has a small and symmetrical dihedral angle(11.9°),which ensures excellent molecular *** aqueous solution,the planar QCy can form closeπ–πmolecular stacking,and fast self-assemble into stable H-aggregates even at low concentrations(1×10−7 M).QCy H-aggregates are sphere-like NPs(QCy NPs)with an average diameter of 120 nm and exhibit high stability.H-aggregation of QCy significantly enhances PCE from 20.1%(non-H-aggregated QCy)to 63.8%(QCy NPs).In addition,the positive charge of quaternarized quinoline provides mitochondrial anchoring ability,which further enhances the photothermal *** high PCE and tumor accumulation,QCy NPs in low-doses have been successfully used in photoacoustic imaging-guided tumor photothermal therapy.

关键词： H-aggregation-enhanced photothermal effect molecular planarity quinoline cyanine mitochondrial anchoring low-dose

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Effect of Hydroxyapatitc Nanoparticles on K562 Cells in vitro

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Journal of Wuhan University of Technology(Materials Science) 2008年第2期23卷 222-224页

作者： CHEN Pei DAI Honglian HAN yingchao yin meizhen LI Shipu Biomedical Materials and Engineering Center Wuhan University of Technology Wuhan 430070 China Nursing school Wuhan Railway Vocational College of Technology Wuhan 430205 China

Stable and single-dispersed hydroxyapatite （HAP） nanoparticles were synthesized with ultrasonic-assisted method. HAP nanoparticles were characterized by dynamic light scattering, XRD （X-ray diffraction） and TEM （Transmission Electron Microscopy）. The effect of HAP nanoparticles on the K562 human myelogenous leukemia cell line was investigated by MTT assay and cell count test, and the mechanism was studied through the changes of cell cycle and ultrastructure. The results showed that HAP nanoparticles inhibited the proliferation of K562 cells dramatically in vitro. HAP nanoparticles entered the cytoplasm of K562 cells and the cells were arrested at G/M phase, thus, the cells died directly.

关键词： hydroxyapatite(HAP) nanoparticles K562 cells MTT assay cell cycle

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Mechanically controlled FRET to achieve high-contrast fluorescence switching

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Science China Chemistry 2018年第12期61卷 1587-1593页

作者： Shenzhong Mo Lina Tan Bing Fang Zhen Wu Zhiqiang Su Yantu Zhang meizhen yin State Key Laboratory of Chemical Resource Engineering Beijing Laboratory of Biomedical Materials Beijing University of Chemical Technology College of Chemistry & Chemical Engineering Yan'an University

Organic luminescent materials with the ability to reversibly switch the luminescence when subjected to external stimuli have attracted considerable interest in recent years. However, luminescent materials with mechanochromic and photochromic dualresponsive properties are rarely reported. Hererin, we designed and synthesized a molecule P1 with dipeptide as a spacer to link rhodamine B and spiropyran moieties. P1 exhibited efficient photochromic properties both in solution and solid state. Highcontrast independent fluorescence switch was also realized under the stimulus of external force. Moreover, two-step ring opening reaction and subsequent fluorescence resonance energy transfer process between the donor-acceptor pairs within one single molecule achieved successive color switch by mechanical control. Therefore, this behavior of P1 made it a promising candidate for high-contrast and sensitive optical recording and mechanical sensing system.

关键词： spiropyran rhodamine B photochromism mechanochromism fluorescence resonance energy transfer

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An AIE Star Polymer with Enhanced Co-Delivery of Drug and Gene for Synergistic Pest Control

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Chinese Journal of Chemistry 2023年第20期41卷 2671-2678页

作者： Bingcheng Zhou Qinhong Jiang Jie Li Shuo Yan Jie Shen Lianying Liu meizhen yin State Key Laboratory of Chemical Resource Engineering Beijing Lab of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing100029 China Department of Plant Biosecurity and MARA Key Laboratory of Surveillance and Management for Plant Quarantine Pests College of Plant ProtectionChina Agricultural UniversityBeijing100193 China

Pesticides,as the most common means of pest managements,have caused a series of problems such as pest resistance and environmental ***-induced emission(AIE)polymers exhibit great potential in biological applications because their fluorescent intensities significantly enhance in the aggregated *** this paper,an AIE star polymer including a tetraphenyl ethylene(TPE)core and poly(2-(dimethylamino)ethyl methacrylate)arms is designed and further developed as a multi-functional nanocarrier for agricultural pest *** nanocarrier shows high water solubility,good size stability and AIE imaging ***,the twisted AIE core and positively charged polymer arms make the nanocarrier efficiently co-load dinotefuran(DIN)and dsRNA via hydrogen bonds and electrostatic interactions,*** AIE star polymer displays low toxicity and high fluorescence *** a result,the nanocarrier co-loading with DIN and dsRNA exhibits a highly synergistic insecticidal effect with higher pest mortality compared to the separate delivery of DIN and *** study develops the AIE star polymer to improve the efficiency of co-delivery of drug and dsRNA and proposes a new strategy toward efficient and synergistic pest control.

关键词： Pest control Nano-delivery system Drug nanocarrier Functional polymers Aggregation-induced emission

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Protective mechanisms of Leontopodium leontopodioides extracts on lipopolysaccharide-induced acute kidney injury via the NF-κB/NLRP3 pathway

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Chinese Journal of Natural Medicines 2023年第1期21卷 47-57页

作者： BAI Xue MA Qianqian LI Qi yin meizhen XIN ying ZHEN Dong WEI Chengxi Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System Inner Mongolia Minzu UniversityTongliao 028000China College of Preventive Medicine Medical CollegeInner Mongolia Minzu UniversityTongliao 028000China Institute of Pharmaceutical Chemistry and Pharmacology Inner Mongolia Minzu UniversityTongliao 028000China College of Traditional Mongolian Medicine Inner Mongolia Minzu UniversityTongliao 028000China

Sepsis-induced uncontrolled systemic inflammatory response syndrome(SIRS)is a critical cause of multiple organ *** kidney injury(AKI)is one of the most serious complications associated with an extremely high mortality rate in SIRS,and it lacked simple,safe,and effective treatment *** leontopodioides(Willd.)Beauv(LLB)is commonly used in traditional Chinese medicine for the treatment of acute and chronic ***,it remains unclear whether lipopolysaccharide(LPS)affects LPS-induced *** identify the molecular mechanisms of LLB in LPS-induced HK-2 cells and mice,LLB was prepared by extraction with 70%methanol,while a lipopolysaccharide(LPS)-induced HK-2 cell model and an AKI model were established in this *** histopathology staining was performed to observe the morphology *** cell supernatant and kidney tissues were collected for determining the levels of inflammatory factors and protein expression by ELISA,immunofluorescence,and Western *** results indicated that LLB significantly reduced the expression of IL-6 and TNF-αin LPS-induced HK-2 cells,as well as the secretion of IL-6,TNF-α,and IL-1βin the *** same results were observed in LPS-induced AKI *** studies revealed that LLB remarkably improved oxidative stress and apoptosis based on the content of MDA,SOD,and CAT in serum and TUNEL staining ***,LLB significantly reduced the mortality due to LPS *** histopathology staining results supported these ***,immunofluorescence and Western blot results confirmed that LLB significantly reduced the expression of the protein related to the NF-κB signaling pathway and NLRP3,ASC,and Caspase-1 which were significantly increased through LPS *** findings clearly demonstrated the potential use of LLB in the treatment of AKI and the crucial role of the NF-κB/NLRP3 pathway in the process through which LLB attenuates AKI induced by LPS.

关键词： Leontopodium leontopodioides Acute kidney injury Ethnopharmacology

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Organic dye assemblies with aggregation-induced photophysical changes and their bio-applications

Aggregate

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Aggregate 2021年第4期2卷 57-71页

作者： Chendong Ji Liming Lai Pengyu Li Zhen Wu Wenyu Cheng meizhen yin State Key Laboratory of Chemical Resource Engineering Beijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijingChina

Phototheranostics provide a safe,effective,and noninvasive way for the diagnosis and treatment of contemporary diseases,and organic dyes play a vital *** example,chemical modification endowed dyes with powerful reactive oxygen species or heat generation ability,favoring for photodynamic therapy and photoacoustic(PA)imaging guided photothermal therapy(PTT)of serious ***,photophysical properties manipulation of dyes has become the focus in current dye chemistry *** development of aggregate science has made great effort to solve this *** recent years,a large number of studies have focused on molecular aggregation behavior and its effect on photophysical *** most famous example is the discovery of aggregation-induced emission(AIE)*** on AIE theory,more theories for revealing the relationship between molecular aggregation behavior and photophysical properties were proposed and *** photophysical property changes caused by dye aggregation have become a unique discipline,guiding the development of molecular science and material *** the help of molecular self-assembly,controllable aggregation of dyes can be realized,and stable nano-theranostic reagents can be ***,constructing dye assemblies with various photophysical properties will greatly reduce the cost of theranostic reagents,thus,expanding biomedical applications of organic ***,this review focuses on the photophysical characteristic changes caused by dye aggregation and their biological applications including,fluorescence/phosphorescence/PA imaging as well as photodynamic and *** review will provide guidance for the design of organic dyes,the development of controllable aggregation methods,and the construction of multifunctional phototheranostic reagents.

关键词： aggregation-induced photophysical changes fluorescence imaging organic dye assemblies phosphorescence photodynamic therapy photothermal therapy

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Synthesis of water-soluble dye-cored poly(amidoamine) dendrimers for long-term live cell imaging

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Science China Materials 2018年第11期61卷 1475-1483页

作者： Yang Cai Chendong Ji Shaobo Zhang Zhiqiang Su meizhen yin State Key Laboratory of Chemical Resource Engineering Beijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing 100029China

Hydrophilic dendrimers, especially poly（amidoamine）（PAMAM） dendrimers are widely applied in modifying fluorescent dyes to endow them with water solubility and biocompatibility for biologic fluorescence *** preparation strategies of fluorescent dendrimers including encapsulating dyes or attaching dyes at periphery of dendrimers might cause uncertain constituent and lower biocompatibility. Here, we have developed a series of watersoluble fluorescent dendrimers with dye as core and fanshaped PAMAM as arms. Carboxylated perylene bisimides（PBI） dye and squarylium indocyanine（SICy） dye were conjugated with PAMAM dendrons by amidation to obtain a series of fluorescent dendrimers with enhanced water-solubility. Two PBI based dendrimers（PBI-G2.5 and PBI-G1.5）were chosen as model compounds for further optical, selfassembly and biological studies. In aqueous environment,PBI-G2.5 exhibited strong fluorescence, small size（~30 nm）and slightly positive surface charge（~2.46 mV）, which are ideal for biomedical applications. In vitro assays demonstrated that PBI-G2.5 nanoparticles accumulated in the cytoplasm of He La cells with rapid cellular uptake. The strong fluorescence in He La cells remained for over 48 h. To conclude, our study provides an effective strategy for preparing water-soluble fluorescent dendrimers towards long-term live cell imaging.

关键词： fluorescent dendrimers fan-shaped PAMAM perylene bisimides water solubility live cell imaging

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Effects of Antihepatocarcinoma with Apatite Nanoparticles in vivo

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Journal of Wuhan University of Technology(Materials Science) 2006年第4期21卷 102-104页

作者：尹美珍李世普 Biomedical Materials and Engineering Center Wuhan University of Technology Wuhan 430070 China

The inhibition effect of hydroxyapatite （ HAP ） nanoparticles on hepatocarcinoma was investigated in vivo. The human hepatocarcinoma cell line Bel- 7402 was transplanted subcutaneously into nude mice. Hydroxyapatite nanoparticles suspension at a dose of 0. 2 mL was injected into the transplanted tumors every day for 2 weeks, and saline was used us control. The efficacy of hydroxyapatite nanoparticles on this carcinoma was surveyed and morphological changes of tissue and cells were observed by light microscopy and transmission electron microscopy （TEM）. Experimental results show that hydroxyapatite nanoparticles have a visible destructive effect on the structures of hepatocarcinoma cells and tissue. The inhibition rates of tumor growth were 77.21% and 51. 32% after intra-tumor injection of hydroxyapatite nanoparticles for 1 week and 2 weeks, respectively. Compared with the control group, hydroxyapatite nanoparticles can also prolong the survival time of the nude mice bearing this cancer significantly. This indicates that hydroxyapatite nanoparticles have the therapeutic potential on hepatoma in vivo.

关键词： hydroxyapatite nanoparticles hepatocarcinoma transplantation nude mice

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