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Multivalent Aptamer-modified DNA Origami as Drug delivery System for Targeted Cancer Therapy

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Chemical Research in Chinese Universities 2020年第2期36卷 254-260页

作者： CAO Mengyao SUN Yueyang XIAO Mingshu LI Li LIU Xiaohui JIN Hong PEI Hao Shanghai Key Laboratory of Green Chemistry and Chemical Processes School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200241E R.China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032P.R.China

In spite of great development in nanoparticle-based drug delivery systems(DDSs)for improved therapeutic efficacy,it remains challenging for effective delivery of chemotherapeutic drugs to targeted tumor *** this work,we report a triangle DNA origami as targeted DDS for cancer *** origami shows excellent biocompatibility and stability in cell culture medium for 24 *** addition,the DNA origami structures conjugated with multivalent aptamers enable for efficient delivery of anticancer drug doxorubicin(Dox)into targeted cancer cell due to their targeting function,reducing side effects associated with nonspecific ***,we also demonstrated that the multivalent aptamer-modified DNA origami loading Dox exhibits prominent therapeutic efficacy in ***,this work provides a good paradigm for the development of DNA origami nanostructure-based targeted DDS for cancer therapy.

关键词： DNA origami Targeted drug delivery system Aptamer

Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system

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Chinese Journal of Natural Medicines 2015年第12期13卷 915-924页

作者： ZHANG Li ZHOU Jian-Ping YAO Jing State Key Laboratory of Natural Medicines Department of PharmaceuticsChina Pharmaceutical University Department of Pharmacy Nanhu Community Health Centre

The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid(HGA) conjugate for intravenous paclitaxel(PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles(PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio(TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.

关键词： Hyaluronic acid Glycyrrhetinic acid Conjugate Synergistically targeted delivery Antitumor activity

Emerging transporter-targeted nanoparticulate drug delivery systems

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Acta Pharmaceutica Sinica B 2019年第1期9卷 49-58页

作者： Hongyan Su Yan Wang Shuo Liu Yue Wang Qian Liu Guangxuan Liu Qin Chen Department of Pharmacy Cancer Hospital of China Medical University Liaoning Cancer Hospital & Institute

Transporter-targeted nanoparticulate drug delivery systems(nano-DDS) have emerged as promising nanoplatforms for efficient drug delivery. Recently, great progress in transporter-targeted strategies has been made, especially with the rapid developments in nanotherapeutics. In this review, we outline the recent advances in transporter-targeted nano-DDS. First, the emerging transporter-targeted nano-DDS developed to facilitate oral drug delivery are reviewed. These include improvements in the oral absorption of protein and peptide drugs, facilitating the intravenous-to-oral switch in cancer chemotherapy. Secondly, the recent advances in transporter-assisted brain-targeting nano-DDS are discussed,focusing on the specific transporter-based targeting strategies. Recent developments in transportermediated tumor-targeting drug delivery are also discussed. Finally, the possible transport mechanisms involved in transporter-mediated endocytosis are highlighted, with special attention to the latest findings of the interactions between membrane transporters and nano-DDS.

关键词： Transporter Nano-DDS Oral delivery Brain-targeting Tumor-targeting

Study on the α-cyclodextrin/poly(ethylene glycol) self-assembly supramolecular nanoparticles for drug delivery

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Science China Chemistry 2010年第3期53卷 495-501页

作者： LI Yuan,JI Li,WANG Gang,SONG LiQing,HE Bin,LI Li,NIE Yu,WU Yao & GU ZhongWei National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610064,China National Engineering Research Center for Biomaterials Sichuan University Chengdu China

This paper reports the synthesis and drug delivery properties of a novel supramolecular nanoparticle.α-Cyclodextrins(α-CD) were threaded on cinnamic acid modified poly(ethylene glycol) to form inclusion complex nanoparticles by supramolecular *** anti-tumor drug doxorubicin was loaded in the nanoparticles and released in vitro to study the drug release behavior and the anti-tumor *** structure and morphology of the nanoparticles were characterized by nuclear magnetic resonance,X-ray diffraction,ultraviolet absorbance,dynamic laser scattering,scanning electronic microscopy,transmission electron microscopy and atom force *** distribution of the drug loaded nanoparticles in cells and the anti-tumor effects were studied by confocal laser *** results demonstrate that the supramolecular nanoparticle is biocompatible and it is a promising carrier for drug delivery systems.

关键词： supramolecular self-assembly nanoparticles drug delivery

A magnetism/laser-auxiliary cascaded drug delivery to pulmonary carcinoma

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1549-1562页

作者： Jialiang Lin Qingqing Yin Binlong Chen Haoran Zhang Dong Mei Jijun Fu Bing He Hua Zhang Wenbing Dai Xueqing Wang Yiguang Wang Qiang Zhang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug delivery Systems School of Pharmaceutical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs Peking UniversityBeijing 100191China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin-biotin interaction with the help of c(RGDfK), magnetic fields and *** ultrasmall superparamagnetic iron oxide nanoparticles(USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin(Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed in vivo that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.

关键词： auxiliary overcome delivery

Self-enhanced targeted delivery of a cell wall– and membrane-active antibiotics,daptomycin, against staphylococcal pneumonia

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Acta Pharmaceutica Sinica B 2016年第4期6卷 319-328页

作者： Hong Jiang Meimei Xiong Qiuyan Bi Ying Wang Chong Li College of Pharmaceutical Sciences Southwest University

Considering that some antibacterial agents can identify the outer structure of pathogens like cell wall and/or cell membrane, we explored a self-enhanced targeted delivery strategy by which a small amount of the antibiotic molecules were modified on the surface of carriers as targeting ligands of certain bacteria while more antibiotic molecules were loaded inside the carriers, and thus has the potential to improve the drug concentration at the infection site, enhance efficacy and reduce potential toxicity. In this study, a novel targeted delivery system against methicillin-resistant Staphylococcus aureus(MRSA)pneumonia was constructed with daptomycin, a lipopeptide antibiotic, which can bind to the cell wall of *** via its hydrophobic tail. Daptomycin was conjugated with N-hydroxysuccinimidyl–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine to synthesize a targeting compound(Dapt–PEG–DSPE) which could be anchored on the surface of liposomes, while additional daptomycin molecules were encapsulated inside the liposomes. These daptomycin-modified, daptomycin-loaded liposomes(DPD-L[D]) showed specific binding to MRSA as detected by flow cytometry and good targeting capabilities in vivo to MRSA-infected lungs in a pneumonia model. DPD-L[D] exhibited more favorable antibacterial efficacy against MRSA than conventional PEGylated liposomal daptomycin both in vitro and in vivo. Our study demonstrates that daptomycin-modified liposomes can enhance MRSAtargeted delivery of encapsulated antibiotic, suggesting a novel drug delivery approach for existing antimicrobial agents.

关键词： Daptomycin Liposome Targeted drug delivery Lung infection Staphylococcus aureus

Agrobacterium-mediated delivery of CRISPR/Cas reagents for genome editing in plants enters an era of ternary vector systems

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Science China(Life Sciences) 2020年第10期63卷 1491-1498页

作者： Yu Zhang Qiang Zhang Qi-Jun Chen State Key Laboratory of Plant Physiology and Biochemistry College of Biological SciencesChina Agricultural UniversityBeijing 100193China Center for Crop Functional Genomics and Molecular Breeding China Agricultural UniversityBeijing 100193China

Lack of appropriate methods for delivery of genome-editing reagents is a major barrier to CRISPR/Cas-mediated genome editing in ***-mediated genetic transformation(AMGT)is the preferred method of CRISPR/Cas reagent delivery,and researchers have recently made great improvements to this *** this article,we review the development of AMGT and AMGT-based delivery of CRISPR/Cas *** give an overview of the development of AMGT vectors including binary vector,superbinary vector,dual binary vector,and ternary vector *** also review the progress in Agrobacterium genomics and Agrobacterium genetic engineering for optimal *** focus in particular on the ternary vector system and the resources we *** summary,it is our opinion that Agrobacterium-mediated CRISPR/Cas genome editing in plants is entering an era of ternary vector systems,which are often integrated with morphogenic *** new vectors described in this article are available from Addgene and/or MolecularCloud for sharing with academic investigators for noncommercial research.

关键词： genome editing CRISPR/Cas ternary vector system delivery Agrobacterium-mediated transformation

Supersaturated polymeric micelles for oral silybin delivery: the role of the Soluplus–PVPVA complex

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Acta Pharmaceutica Sinica B 2019年第1期9卷 107-117页

作者： Chunliu Zhu Shuang Gong Jinsong Ding Miaorong Yu Ejaj Ahmad Yi Feng Yong Gan Engineering Research Center of Modern Preparation Technology of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Shanghai Institute of Materia Medica Chinese Academy of Science Xiangya School of Pharmaceutical Science Central South University

Increasing the degree of supersaturation of drugs and maintaining their proper stability are very important in improving the oral bioavailability of poorly soluble drugs by a supersaturated drug delivery system(SDDS). In this study, we reported a complex system of Soluplus–Copovidone(Soluplus–PVPVA)loaded with the model drug silybin(SLB) that could not only maintain the stability of a supersaturated solution but also effectively promote oral absorption. The antiprecipitation effect of the polymers on SLB was observed using the solvent-shift method. In addition, the effects of the polymers on absorption were detected by cellular uptake and transport experiments. The mechanisms by which the Soluplus–PVPVA complex promotes oral absorption were explored by dynamic light scattering, transmission electron microscopy, fluorescence spectra and isothermal titration calorimetry analyses. Furthermore, a pharmacokinetic study in rats was used to demonstrate the advantages of the Soluplus–PVPVA complex. The results showed that Soluplus and PVPVA spontaneously formed complexes in aqueous solution via the adsorption of PVPVA on the hydrophilichydrophobic interface of the Soluplus micelle, and the Soluplus–PVPVA complex significantly increased the absorption of SLB. In conclusion, the Soluplus–PVPVA complex is a potential SDDS for improving the bioavailability of hydrophobic drugs.

关键词： Silybin Soluplus PVPVA Complex Supersaturated drug delivery system Oral bioavailability

Analysis of environmental impacts of drone delivery on an online shopping system

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Advances in Climate Change Research 2018年第3期9卷 201-207页

作者： Jarotwan KOIWANIT Faculty of Engineering King Mongkut's Institute of Technology Ladkrabang Bangkok 10520 Thailand

In rural areas, drones are designed to replace road deliveries so as to overcome infrastructure challenges; though drones notably consume lessfuel and consequently have a smaller impact on the environment, their full life cycle assessment should still be evaluated to comprehensivelyunderstand their environmental impact. This study presents a life cycle assessment study on drone delivery in Thailand using CML2001, the lifecycle impact assessment （LCIA） method, to convert life cycle inventory data into environmental impacts. The observed results show that anonline shopping system using drone delivery is one of the most environmentally friendly transportation options throughout a wide range ofscenarios. However, the parts production contributed to significant impacts on environmental issues while the drone operation showed the leastimpact to all impact categories. The dominant contributors to global warming, abiotic depletion （ADP elements and fossil）, acidification air,eutrophication, ozone layer depletion, and photochemical ozone creation impact categories were the coal mining and electricity generatingstation operation. However, the carbon fibers and the battery, are the main contributors to other impact categories, which include the humantoxicity, freshwater aquatic ecotoxicity, marine aquatic ecotoxicity, and terrestric ecotoxicity.

关键词： LCA GHG emissions CML2001 Online shopping Drone delivery