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Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleicacid drugs: learning from virus

Vaibhav Mundra, Ram I. Mahato

《化学科学与工程前沿（英文）》 2014年 第8卷 第4期   页码 387-404 doi: 10.1007/s11705-014-1457-3

摘要： There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocarriers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intracellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake pathways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocarriers for efficient cellular uptake and endosomal escape.

关键词： nanocarrier     cellular uptake     endosomal release     nucleic acid drug    

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Nucleic acid crystallization and X-ray crystallography facilitated by single selenium atom

Wen Zhang,Jack W. Szostak,Zhen Huang

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 196-202 doi: 10.1007/s11705-016-1565-3

摘要： X-ray crystallography is a powerful strategy for 3-D structure determination of macromolecules, such as nucleic acids and protein-nucleic acid complexes. However, the crystallization and phase determination are the major bottle-neck problems in crystallography. Recently we have successfully developed synthesis and strategy of selenium-derivatized nucleic acids (SeNA) for nucleic acid crystallography. SeNA might not only provide the rational strategies to solve the phase determination problem, but also offer a potential strategy to explore crystallization solutions.

关键词： selenium     DNA     RNA     nucleic acid     crystallization    

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Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 116-122 doi: 10.1007/s11705-013-1310-0

摘要： Polymethacrylic acid (PMA) was synthesized on the backbone of psyllium (Psy) by a microwave assisted method to prepare polymeric grafted materials designated as (Psy- -PMA). Various grades of Psy- -PMA were prepared by changing the degree of grafting from 35%–58% and the materials were then made into tablets. Swelling and biodegradability studies of the tablets were carried out. Acetyl salicylic acid was incorporated in the various Psy- -PMA samples and tablets were prepared to study the in vitro drug release in acidic (pH= 4), neutral (pH= 7), and basic (pH= 9) media. In the acidic medium, the swelling was more than 1300%. In addition, the biodegradable Psy- -PMA had the highest drug release in the acidic medium. This may be attributed to Fickian diffusion since the drug and the medium in which it was released have the same acidic nature.

关键词： psyllium     acetyl salicylic acid     in-vitro drug release     swelling     biodegradation    

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Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers

Ulrich L?CHELT, Ernst WAGNER

《化学科学与工程前沿（英文）》 2011年 第5卷 第3期   页码 275-286 doi: 10.1007/s11705-011-1203-z

摘要： Polymer-based conjugates are an interesting option and challenge for the design of nano-sized drug-delivery systems, as they require advanced conjugation chemistry and precise engineering. In the case of nucleic acid therapy, non-viral carriers face several biological barriers during the delivery process, namely 1) protection of the cargo from extracellular degradation, 2) avoidance of non-specific interactions with non-targeted tissues, 3) efficient entry into the target cells, 4) intracellular trafficking to the site of action and 5) cargo release. To take on these obstacles, multifunctional conjugates can act as “smart polymers” with microenvironment-sensing dynamics to facilitate the separate delivery steps. Synthesis of defined polymer architectures with precise functionalization enables structure-activity relationships to be investigated and the integration of key functions for efficient delivery. Thus bioresponsive polymer conjugates, which are equipped with molecular devices responding to the certain microenvironments within the delivery pathway (e.g. pH, redox potential, enzymes) can be assembled. This review focuses on the modular engineering and conjugation of multifunctional polymeric structures for the utilization as “tailor-made” nucleic acid carriers.

关键词： conjugate     DNA     gene transfer     polymer     RNA     targeting    

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Validation of polarizable force field parameters for nucleic acids by inter-molecular interactions

Liaoran Cao,Hong Ren,Jing Miao,Wei Guo,Yan Li,Guohui Li

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 203-212 doi: 10.1007/s11705-016-1572-4

摘要： Modeling structural and thermodynamic properties of nucleic acids has long been a challenge in the development of force fields. Polarizable force fields are a new generation of potential functions to take charge redistribution and induced dipole into account, and have been proved to be reliable to model small molecules, polypeptides and proteins, but their use on nucleic acids is still rather limited. In this article, the interactions between nucleic acids and a small molecule or ion were modeled by AMOEBAbio09, a modern polarizable force field, and conventional non-polarizable AMBER99sb and CHARMM36 force fields. The resulting intermolecular interaction energies were compared with those calculated by ab initio quantum mechanics methods. Although the test is not sufficient to prove the reliability of the polarizable force field, the results at least validate its capability in modeling energetics of static configurations, which is one basic component in force field parameterization.

关键词： nucleic acid     polarizable force field     AMOEBA    

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Nucleic acid-based diagnostics for infectious diseases in public health affairs

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 173-186 doi: 10.1007/s11684-012-0195-5

摘要：

Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.

关键词： nucleic acid-based diagnostics     infectious disease     PCR     NASBA     LAMP     microarray     LOAC     public health affairs    

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Controlled drug release of 5-amino salicylic acid by poly(2-hydroxyethylmethacrylate) grafted agar

G. Usha RANI,Kartick Prasad DEY,Srijita BHARTI,Sumit MISHRA

《化学科学与工程前沿（英文）》 2014年 第8卷 第4期   页码 465-470 doi: 10.1007/s11705-014-1452-8

摘要： The utilization of poly (2-hydroxyethylmethacrylate) grafted agar (Ag-g-P(HEMA)) as a matrix for the controlled release of 5-aminosalicylic acid was investigated. Grafted copolymers of 2-hydroxyethylmethacrylate (HEMA) monomers on agar were synthesized by microwave assisted method. drug release studies were performed at pH values of 2 and 7 in order to investigate the possibility of pH triggered release for colon targeted drug delivery. Further, the percent grafting . (the time taken for release of 50% of the enclosed drug) value was studied and the results indicate that it may be possible to develop a programmable drug release matrix based on grafted polysaccharide. Ag-g-P(HEMA) appears to be a useful matrix for controlled release.

关键词： agar     controlled drug release     5-Amino salicylic acid     poly(2-hydroxyethylmethacrylate) grafted agar    

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核酸疫苗研发态势与发展建议

李爱花,杨雪梅,孙轶楠,苑亚坤,杨俊涛

《中国工程科学》 2021年 第23卷 第4期   页码 153-161 doi: 10.15302/J-SSCAE-2021.04.018

摘要：

应对新型冠状病毒肺炎（COVID-19）疫情防控的迫切需求，核酸疫苗以其快速高效的优点得到了疫苗研发领域的高度重视，特别是信使核糖核酸（mRNA）疫苗的研发进程显著加快，首次获批上市并在人体中使用。本文从核酸疫苗及相关技术概念、研发轨迹与发展趋势等方面总结梳理核酸疫苗的研发态势，辨识核酸疫苗特征，分析 COVID-19 疫情对 mRNA疫苗研究的促进作用，梳理核酸疫苗拓展应用的主要领域，针对可能存在的技术性、安全性问题开展深入讨论。研究建议，从改良目的基因表达、完善递送系统、提高免疫应答、增强 mRNA 稳定性及易存性等方面着手，着力开展核酸疫苗的关键技术开发；严格监管核酸疫苗的安全性和有效性；引导利益相关方对具有安全性风险、可能对肿瘤与传染病防控带来颠覆性影响的 mRNA 疫苗技术开展改进研究，注重技术研发的前瞻布局并促进应用转化。

关键词： 核酸疫苗     脱氧核糖核酸（DNA）疫苗     核糖核酸（RNA）疫苗     信使核糖核酸（mRNA）疫苗     新型冠状病毒肺 炎     肿瘤    

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Flow cytometric assessment of the effects of chlorine, chloramine, and UV on bacteria by using nucleicacid stains and 5-cyano-2,3-ditolyltetrazolium chloride

Xuebiao Nie, Wenjun Liu, Mo Chen, Minmin Liu, Lu Ao

《环境科学与工程前沿（英文）》 2016年 第10卷 第6期 doi: 10.1007/s11783-016-0884-4

摘要： Flow cytometry based on nucleic acid stains and CTC was established and optimized. Membrane of is more resistant to chlorine/chloramine than . The metabolic activity of bacteria persisted after the cytomembranewas damaged. showed more resistance to UV irradiation than by FCM. MP-UV was a stronger inhibitor of metabolic activity than LP-UV. Flow cytometry (FCM) has been widely used in multi-parametric assessment of cells in various research fields, especially in environmental sciences. This study detected the metabolic activity of and by using an FCM method based on 5-cyano-2,3-ditolyltetrazolium chloride (CTC); the accuracy of this method was enhanced by adding SYTO 9 and 10% R2A broth. The disinfection effects of chlorine, chloramine, and UV were subsequently evaluated by FCM methods. Chlorine demonstrated stronger and faster destructive effects on cytomembrane than chloramine, and nucleic acids decomposed afterwards. The metabolic activity of the bacteria persisted after the cytomembranewas damaged as detected using CTC. Low-pressure (LP) UV or medium-pressure (MP) UV treatments exerted no significant effects on membrane permeability. The metabolic activity of the bacteria decreased with increasing UV dosage, and MP-UV was a stronger inhibitor of metabolic activity than LP-UV. Furthermore, the membrane of Gram-positive was more resistant to chlorine/chloramine than that of Gram-negative . In addition, showed higher resistance to UV irradiation than .

关键词： Flow cytometry     Escherichia coli     Staphylococcusaureus     UV     CTC     SYTO 9    

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Taking advantage of drug resistance, a new approach in the war on cancer

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 490-495 doi: 10.1007/s11684-018-0647-7

摘要：

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.

关键词： cancer     drug resistance     genetic screens     senescence     targeted therapy    

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Protein microspheres for pulmonary drug delivery

Yongda SUN,

《化学科学与工程前沿（英文）》 2010年 第4卷 第1期   页码 82-86 doi: 10.1007/s11705-009-0307-1

摘要： A new supercritical fluid (SCF) technique was developed for the preparation of microspheres for pulmonary drug delivery (PDD). This technique, based on the anti-solvent process, has incorporated advanced engineering design features to enable improved control of the particle formation process. Human recombinant insulin (HRI) was used as a model compound to evaluate the efficiency of this SCF process. An aqueous solution of HRI with a co-solvent was sprayed into high pressure carbon dioxide that extracted the solvent and water, leading to a dry fine powder with good particle size distribution and near ideal morphology for pulmonary drug delivery.

关键词： advanced engineering     improved     pressure     aqueous     technique    

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Semi-solid materials for controlled release drug formulation: current status and future prospects

Michelle TRAN,Chun WANG

《化学科学与工程前沿（英文）》 2014年 第8卷 第2期   页码 225-232 doi: 10.1007/s11705-014-1429-7

摘要： Semi-solid materials represent an important category of inactive ingredients (excipients) of pharmaceutical products. Here we review several common semi-solid polymers currently used in the controlled release formulations of many drugs. These polymers are selected based on their importance and broad scope of application in FDA-approved drug products and include several polysaccharides (cellulose, starch, chitosan, alginate) and carbomers, a group of mucoadhesive synthetic polymers. Glyceride-based polymers used in self-emulsifying drug delivery systems (SEDDS) will also be discussed for its importance in formulating poorly water-soluble drugs. Unique features and advantages of each type of semi-solid materials are discussed and examples of their use in oral delivery of drugs are provided. Finally, future prospects of developing new and better semi-solid excipients are discussed with the objective of facilitating clinical translation.

关键词： controlled release     drug delivery     semi-solids     polymer     excipient    

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Nanostructured hollow spheres of hydroxyapatite: preparation and potential application in drug delivery

Xiaojing ZHANG, Weixin ZHANG, Zeheng YANG, Zhao ZHANG

《化学科学与工程前沿（英文）》 2012年 第6卷 第3期   页码 246-252 doi: 10.1007/s11705-012-1299-9

摘要： A solvothermal method has been successfully used to prepare nanostructured hydroxyapatite (HA) hollow spheres with average diameters of about 500 nm and shell thicknesses of about 100 nm in a glycerin/water mixed solvent. Transmission electron microscopy (TEM) and field-emission scanning electron microscopy (FESEM) images show that the shells of the HA hollow spheres are actually composed of nanosheets with thicknesses of about 10 nm. By tuning the glycerin/water volume ratio, two other kinds of HA solid spheres with average diameters of about 6 or 20 μm were assembled from nanoflakes. The properties of the different kinds of spheres as drug delivery carriers were evaluated. Ibuprofen (IBU) was chosen as the model drug to load into the HA samples. The nanostructured HA samples showed a slow and sustained release of IBU. The HA hollow spheres exhibited a higher drug loading capacity and more favorable release properties than the HA solid spheres and thus are very promising for controlled drug release applications.

关键词： hydroxyapatite     hollow spheres     synthesis     drug release    

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Prevalence of antifolate drug resistance markers in in China

《医学前沿（英文）》 2022年 第16卷 第1期   页码 83-92 doi: 10.1007/s11684-021-0894-x

摘要： The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax and antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009–2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.

关键词： drug resistance     antifolates     molecular markers     Plasmodium vivax     China    

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标题 作者 时间 类型 操作

Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleicacid drugs: learning from virus

Vaibhav Mundra, Ram I. Mahato

期刊论文

Nucleic acid crystallization and X-ray crystallography facilitated by single selenium atom

Wen Zhang,Jack W. Szostak,Zhen Huang

期刊论文

Biodegradable polymethacrylic acid grafted psyllium for controlled drug delivery systems

Ranvijay KUMAR, Kaushlendra SHARMA

期刊论文

Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers

Ulrich L?CHELT, Ernst WAGNER

期刊论文

Validation of polarizable force field parameters for nucleic acids by inter-molecular interactions

Liaoran Cao,Hong Ren,Jing Miao,Wei Guo,Yan Li,Guohui Li

期刊论文

Nucleic acid-based diagnostics for infectious diseases in public health affairs

null

期刊论文

Controlled drug release of 5-amino salicylic acid by poly(2-hydroxyethylmethacrylate) grafted agar

G. Usha RANI,Kartick Prasad DEY,Srijita BHARTI,Sumit MISHRA

期刊论文

核酸疫苗研发态势与发展建议

李爱花,杨雪梅,孙轶楠,苑亚坤,杨俊涛

期刊论文

Flow cytometric assessment of the effects of chlorine, chloramine, and UV on bacteria by using nucleicacid stains and 5-cyano-2,3-ditolyltetrazolium chloride

Xuebiao Nie, Wenjun Liu, Mo Chen, Minmin Liu, Lu Ao

期刊论文

Taking advantage of drug resistance, a new approach in the war on cancer

null

期刊论文

李爱花：基于数据视角的核酸疫苗研发态势与发展建议（2021年9月3日）

2021年10月15日

会议视频

Protein microspheres for pulmonary drug delivery

Yongda SUN,

期刊论文

Semi-solid materials for controlled release drug formulation: current status and future prospects

Michelle TRAN,Chun WANG

期刊论文

Nanostructured hollow spheres of hydroxyapatite: preparation and potential application in drug delivery

Xiaojing ZHANG, Weixin ZHANG, Zeheng YANG, Zhao ZHANG

期刊论文

Prevalence of antifolate drug resistance markers in in China

期刊论文