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Fabrication of self-assembling nanofibers with optimal cell uptake and therapeutic delivery efficacy

Bioactive Materials 2017年第4期2卷 260-268页

作者： Dawei Xu Damien SKSamways He Dong Department of Chemistry&Biomolecular Science Clarkson UniversityPotsdamUSA Department of Biology Clarkson UniversityPotsdamUSA

Effective strategies to fabricate finite organic nanoparticles and understanding their structure-dependent cell interaction is highly important for the development of long circulating nanocarriers in cancer therapy.In this contribution,we will capitalize on our recent development of finite supramolecular nanofibers based on the self-assembly of modularly designed cationic multidomain peptides(MDPs)and use them as a model system to investigate structure-dependent cell penetrating activity.MDPs selfassembled into nanofibers with high density of cationic charges at the fiber-solvent interface to interact with the cell membrane.However,despite the multivalent charge presentation,not all fibers led to high levels of membrane activity and cellular uptake.The flexibility of the cationic charge domains on self-assembled nanofibers plays a key role in effective membrane perturbation.Nanofibers were found to sacrifice their dimension,thermodynamic and kinetic stability for a more flexible charge domain in order to achieve effective membrane interaction.The increased membrane activity led to improved cell uptake of membrane-impermeable chemotherapeutics through membrane pore formation.In vitro cytotoxicity study showed co-administering of water-soluble doxorubicin with membrane-active peptide nanofibers dramatically reduced the IC50 by eight folds compared to drug alone.Through these detailed structure and activity studies,the acquired knowledge will provide important guidelines for the design of a variety of supramolecular cell penetrating nanomaterials not limited to peptide assembly which can be used to probe various complex biological processes.

关键词： Supramolecular assembly cell penetrating peptide Drug delivery cell uptake Membrane activity

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Mitochondria-targeted cancer therapy based on functional peptides

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Chinese Chemical Letters 2023年第5期34卷 104-110页

作者： Yuhan Sun He Zhang Guangzhao Lu Huan Wang Ying Lu Li Fan Department of Pharmaceutical Sciences School of PharmacyNaval Medical UniversityShanghai 200433China

Mitochondria are critical for tumor growth and metastasis.A number of traditional antitumor drugs have poor water solubility and must penetrate multiple cellular barriers to reach the mitochondria.Because mitochondria have a unique transmembrane potential and an inner membrane with a low permeability,it is difficult for most drugs to enter mitochondria.In recent years,mitochondria-targeted delivery systems that use functional peptides to modify drugs have received increasing attention.Introducing functional peptides can change the original physicochemical properties of drugs and actively target mitochondria.Functional peptide-drug conjugates(PDCs,peptide-drug conjugates)can decompose and release drugs over time or due to certain stimuli in tumors.This preserves the biological activity of the drug while increasing intratumor uptake through the enhanced permeability and retention effect(EPR,the enhanced permeability and retention effect).In this review,we focus on the direction of cancer therapy and review the application of different functional peptides in the mitochondria-targeted tumor treatments reported in recent years.

关键词： Peptides Mitochondria Cancer therapy Targeting cell uptake

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Reducing systemic absorption and macrophages clearance of genistein by lipid-coated nanocrystals for pulmonary delivery

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Chinese Chemical Letters 2023年第1期34卷 245-250页

作者： Yuan He Chang Liu Run Han Yingmin Liang Judith Choi Wo Mak Yinghao Zhu Haifeng Li Ying Zheng State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina Department of Pharmacy Xuzhou Medical UniversityXuzhou 221004China LKS Faculty of Medicine Department of MedicineThe University of Hong KongHong KongChina Institute of Applied Physics and Materials Engineering University of MacaoMacaoChina

Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory diseases.However,the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the lung.In this study,we designed a lipid-coated genistein nanocrystals(Lipo-NCs)formulation to achieve enhanced efficiency of local pulmonary delivery.The LipoNCs were fabricated by modifying genistein nanocrystals(NCs)with phospholipid membrane through thin film hydration following the homogenization method.The prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked NCs.Our results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid coating.Furthermore,the macrophages clearance was also impeded by this Lipo-NCs formulation.In vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of Lipo-NCs.The pharmacokinetic study displayed that the AUC((0-t))values of Lipo-NCs were 1.59-fold lesser than those of the NCs group,indicating a reduced systemic absorption.In conclusion,this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance,and thus enhancing drug concentration in lung by pulmonary delivery.

关键词： Pulmonary delivery Lipid-coated nanocrystals cell uptake Transport Systemic absorption Macrophage clearances

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Impact of particle size and pH on protein corona formation of solid lipid nanoparticles:A proof-of-concept study

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Acta Pharmaceutica Sinica B 2021年第4期11卷 1030-1046页

作者： Wenhao Wang Zhengwei Huang Yanbei Li Wenhua Wang Jiayu Shi Fangqin Fu Ying Huang Xin Pan Chuanbin Wu School of Pharmaceutical Sciences Sun Yat-Sen UniversityGuangzhou 510006China College of Pharmacy Jinan UniversityGuangzhou 511443China

When nanoparticles were introduced into the biological media,the protein corona would be formed,which endowed the nanoparticles with new bio-identities.Thus,controlling protein corona formation is critical to in vivo therapeutic effect.Controlling the particle size is the most feasible method during design,and the infuence of media pH which varies with disease condition is quite important.The impact of particle size and pH on bovine serum albumin(BSA)corona formation of solid lipid nanoparticles(SLNs)was studied here.The BSA corona formation of SLNs with increasing particle size(120-480 nm)in pH 6.0 and 7.4 was investigated.Multiple techniques were employed for visualization study,conformational structure study and mechanism study,etc."BSA corona-caused aggregation"of SLN2-3 was revealed in pH 6.0 while the dispersed state of SLNs was maintained in pH 7.4,which signifcantly affected the secondary structure of BSA and cell uptake of SLNs.The main interaction was driven by van der Waals force plus hydrogen bonding in p H 7.4,while by electrostatic attraction in pH 6.0,and size-dependent adsorption was confrmed.This study provides a systematic insight to the understanding of protein corona formation of SLNs.

关键词： Protein corona Solid lipid nanoparticles BSA corona-Caused aggregation Nanoparticle-protein interaction Size effect cell uptake Medium pH Conformational structure

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Surface-ligand effect on radiosensitization of ultrasmall luminescent gold nanoparticles

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Journal of Innovative Optical Health Sciences 2016年第4期9卷 66-73页

作者： Xingya Jiang Bujie Du Mengxiao Yu Xun Jia Jie Zheng Department of Chemistry and Biochemistry The University of Texas at Dallas 800 W.Campbell Rd. RichardsonTX 75080USA Department of Radiation Oncology The University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard DallasTX 75390USA

Gold nanoparticles(AuNPs)could serve as pot ential radiother apy sensitizers because of their exceptional biocompatibility and high.Z material nature;however,since in vitro and in vivo behaviors of AuNPs are determined not only by their particle size but also by their surface chemistries,whether surface ligands can affect their radiosensitization has seldom been investi-gated in the radiosensitization of AuNPs.By conducting head-to-head comparison on radio-sensitization of two kinds of ultrasmall(~2 nm)near-infrared(NIR)emitting AuNPs that are coated with zwitterionic glutathione and neutr al polyethylene glyol(PEG)ligands,respectively,we found that zwitterionic glut athione coated AuNPs(GS-AuNPs)can reduce survival rates of MCF-7 cells under irr adiation of clinically used megavoltage photon beam at low dosage of~2.25 Gy.On the other hand,PEG-AuNPs can serve as a radiation-protecting agent and enabled MCF-7 cells more resistant to the irradiation,clearly indicating the key role of surface cheistry in radiosensitization of AuNPs.More detailed studies suggested that such difference was inde-pendent of cellular uptake and its eficiency,but might be related to the ligand-induced difference in photoelectron generation and/or inter actions between AuNPs and X-ray triggered reactive oxygen species(ROS).

关键词： Gold nanoparticles surface-ligand cell uptake radiosensitizer radiation-protecting

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Fe3O4 encapsulated mesoporous silica nanospheres with tunable size and large void pore

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Frontiers of Chemical Science and Engineering 2014年第1期8卷 114-122页

作者： Tingting LIU Lihong LIU Jian LIU Shaomin LIU Shi Zhang QIAO Department of Chemical Engineering Curtin University Perth WA 6845 Australia School of Chemical Engineering The University of Adelaide SA5005 Australia

Magnetic Fe3O4 and mesoporous silica core- shell nanospheres with tunable size from 110-800 nm were synthesized via a one step self-assembly method. The morphological, structural, textural, and magnetic proper- ties were well-characterized by scanning electron micro- scopy, transmission electron microscopy, X-ray diffraction, N2 adsorption-desorption and magnetometer. These nanocomposites, which possess high surface area, large pore volume and well-defined pore size, exhibit two dimensional hexagonal （P6mm） mesostructures. Interest- ingly, magnetic core and mesoporous silica shell nano- composites with large void pore （20 nm） on the shell were generated by increasing the ratio of ethanol/water. Additionally, the obtained nanocomposites combined magnetization response and large void pore, implying the possibility of applications in drug/gene targeting delivery. The cell internalization capacity of NH2-functionalized nanocomposites in the case of cancer cells （HeLa cells） was exemplified to demonstrate their nano-medicine application.

关键词： mesoporous silicas magnetic nanoparticles,core-shell nanoparticles cell uptake

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A Comparative Study of ^(99m)Tc-YIGSR and 99mTc-MIBI uptake in Tumor cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2005年第6期25卷 712-714页

作者：胡佳兰晓莉张永学高再荣伍军 Department of Nuclear Medcine Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

To investigate a new kind of tumor tracer ^99mTc-YIGSR developed from a five amino structure （YIGSR） of the Laminin -chain, which can bind to the laminin receptors of tumor specifically, and radiolabeled with MAG3. （1） Preparation of the ^99mTc-YIGSR probe： with S-Acetly-NH3- MAG3as the chelator and with proper reductants YIGSR was labeled with ^99mTc;（2） cell culture and viability measurement： EAC was maintained in RPMI 1640 supplemented with calf serum; the trypan blue exclusion was applied to calculate the cell viability; （3） Study of the cell dynamic： The EAC＇s uptake of ^99mTc-YIGSR and ^99mTc-MIBI was observed at 37℃ and 22 ℃, respectively. （1） The labeling efficiencies of ^99mTc-YIGSR and^99mTc-MIBI were （62±3） % and （96±2） %, respectively; （2） The cell viability was declined with time of incubation; （3） At 37 ℃, the EAC＇S uptake of ^99mTc YIGSR and^99mTc-MIBI reached the peak of （43. 16±2.4） % and （24.4±1.8） % at 60 min, respectively; and at 22 ℃, the highest uptake was （26.5±2. 1） % and （9.47±1.9） % at 60 min, respectively. The in vitro study suggests that ^99mTc-YIGSR is superior to ^99mTc-MIBI in cell uptake and has potential value in tumor imaging.

关键词： laminin-YIGSR methoxyisobuty （MIBI-lisonitrile） tumor cell uptake ^99mTc

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Two Dimensional Nanoparticles Induce cell Autophagy without Being Internalized

Two Dimensional Nanoparticles Induce Cell Autophagy without ...

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全国环境纳米技术及生物效应学术研讨会

作者： Xiaofei Zhou Chang Liu Bing Yan School of Chemistry and Chemical Engineering Shandong University

Two dimensional nanosheets are promising in biomedical, bio-sensing, electronic and photothermal therapy applications. It is possible that two dimensional nanoparticles（2D NPs） from materials used in biomedical fields may enter human body directly. 2D NPs may also be released from various devices and contaminate air and water. Toxicity caused by these environmental particles cannot be avoided. Thus the behavior of 2D NPs in biological system needs urgent attention. So far, very little is known how well dispersed 2D NPs interact with cells. In this work, interactions between two dimensional MoS2 and WS2 NPs and human cells were investigated. Transmission electron microscopy observations, confocal laser scanning microscopy examinations, and ICP-MS analysis of cellular content showed that these 2D NPs were mainly bound to cell surface without being internalized. Surface bindings by these 2D NPs did not induce cytotoxicity or apoptosis, but induced cell autophagy, as observed by the induction of autophagy flux and the formation of autophagosomes. The detection of p-mTOR and p-p70 S6 K protein level showed that autophagy induced by MoS2 or WS2 nanoparticles was mTOR-independent. These experimental findings and mechanism investigations will be reported.

关键词： MoS2 WS2 nanosheet autophagy cell uptake

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Peptides:prospective gene delivery vehicles

Peptides:prospective gene delivery vehicles

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华东六省一市生物化学与分子生物学会2008年学术交流会

作者： ~1Lu Yanqin ~1Han Jingxiang ~2 Pavia Simerska ~2Istvan Toth ~2 Rodney Minchin (1:Shandong Medicinal Biotechnology Centre,Shandong Academy of Medical Sciences,Jinan 250062 2:University of Queensland,Brisbane 4067)

Gone therapy is a promising tool for curing various human diseases by introducing a therapeutic gene to replace or correct a defective gene.Gene delivery is the biggest challenge of gene therapy.Gene transfer vectors can be divided into two classes.Viral and non-viral systems. The percentage of gene therapy clinical trials employ non-viral vectors is increasing because they are relative safe,simple to prepare and little toxic. Initially,peptide was used for drug delivery.Recently,it has been utilized in the field of gene transfer.Here,three types of peptides were combined to improve the cellular uptake and transgene expression.Polylysine was one of the fast polycations used in gene delivery because of its high condensation ability.Membrane-penetrating peptide derived from HIV transactivator Tat and penetratin from Antermapedia,a Drosophila transcription factor had shown efficient transfer of nucleic acids by destablizating the cell membrane.nuclear location signal(NLS)from SV40 T antigen was believed to enhance the import of transgene.Seven carriers with various combinations of short peptides TAT,penetratin,PLL,NLS and lipids were designed,synthesized and their potential ability as gene delivery tools were assessed. Firstly,The DNA condensation ability of seven carriers was compared by agarose gel shift assay by using pGL3-Control plasmid DNA.Then,cell cytotoxicity of seven carries was evaluated by cell viability assay.cellular uptake were evaluated by labeling plasmid DNA with YOYO-ldye, the P/N charge ratio(carries/plasmid DNA)of 1,5,10 and 20 were utilized to cell transfection and uptake efficiency was assessed by f flow cytometry analysis.At last,expression of luciferease reporter was analyzed by luciferease assay. The migration of all DNA-carriers complexes was completely retarded below the P/N ratio of 2. 4TAT-NLS-2C12 displayed the strongest ability to condense DNA.Penetratin-derived peptide showed lower toxicity than that of tat-derived.Tat derived peptide showed a little higher uptake than penetratin,as

关键词： Peptide gene delivery gene expression cell uptake gel shift

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Studies on the bio-character of a new pH-sensitive doxorubicin prodrug using LC-MS/MS method

Studies on the bio-character of a new pH-sensitive doxorubic...

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第八届全国化学生物学学术会议

作者： Ruixing Zhang Fengrui Sonng Chemical Biology Laboratory ＆ Changchun Center of Mass Spectrometry Changchun Institute of Applied ChemistryChinese Academy of Sciences

＜正＞Tiffs study was focus on the release and cell uptake of a new pH-sensitive doxorubicin prodmgm PEG-P（LA-co-DHP/DOX）.The release of Dox form prodrug was studied at 37℃in three different media,that is, acetate buffer at pH 5.0,pH6.5 and pH7.4,respectively.The results showed that about 80%of Dox was released from P（Dox）in the pH 5.0 acetate buffer in 48 h,and in the same time duration only 20%in pH 6.5 acetate buffer

关键词： Doxorubicin prodrug LC-MS/MS pH-sensitive cell uptake

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