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Novel lysosome-targeted anticancer fluorescent agents used in zebrafish and nude mouse tumour imaging

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 112-120 doi: 10.1007/s11705-021-2075-5

摘要： The design of three novel fatty nitrogen mustard-based anticancer agents with fluorophores incorporated into the alkene structure (CXL 118, CXL121, and CXL122) is described in this report. The results indicated that these compounds are selectively located in lysosomes and exhibit effective antitumour activity. Notably, these compounds can directly serve as both reporting and imaging agents in vitro and in vivo without the need to add other fluorescent tagging agents.

关键词： fluorescent drug lysosomal anticancer zebrafish nude-mouse tumour imaging

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Information gathering and processing with fluorescent molecules

Brian DALY,Jue LING,A. Prasanna de SILVA

《化学科学与工程前沿（英文）》 2014年第8卷第2期页码 240-251 doi: 10.1007/s11705-014-1432-z

摘要： Molecular information gathering and processing — a young field of applied chemistry — is undergoing good growth. The progress is occurring both in terms of conceptual development and in terms of the strengthening of older concepts with new examples. This review critically surveys these two broad avenues. We consider some cases where molecules emulate one of the building blocks of electronic logic gates. We then examine molecular emulation of various Boolean logic gates carrying one, two or three inputs. Some single-input gates are popular information gathering devices. Special systems, such as ‘lab-on-a-molecule’ and molecular keypad locks, also receive attention. A situation deviating from the Boolean blueprint is also discussed. Some pointers are offered for maintaining the upward curve of the field.

关键词： molecular logic molecular computation molecular sensor fluorescent molecular device fluorescent sensor

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Recent advances of small-molecule fluorescent probes for detecting biological hydrogen sulfide

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 34-63 doi: 10.1007/s11705-021-2050-1

摘要： H₂S is well-known as a colorless, acidic gas, with a notoriously rotten-egg smell. It was recently revealed that H₂S is also an endogenous signaling molecule that has important biological functions, however, most of its physiology and pathology remains elusive. Therefore, the enthusiasm for H₂S research remains. Fluorescence imaging technology is an important tool for H₂S biology research. The development of fluorescence imaging technology has realized the study of H₂S in subcellular organelles, facilitated by the development of fluorescent probes. The probes reviewed in this paper were categorized according to their chemical mechanism of sensing and were divided into three groups: H₂S reducibility-based probes, H₂S nucleophilicity-based probes, and metal sulfide precipitation-based probes. The structure of the probes, their sensing mechanism, and imaging results have been discussed in detail. Moreover, we also introduced some probes for hydrogen polysulfides.

关键词： hydrogen sulfide fluorescent probe reducibility nucleophilicity copper sulfide precipitate hydrogen polysulfides

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Fluorescent properties and

Hong GAO,Jie SONG,Shibin SHANG,Zhanqian SONG

《农业科学与工程前沿（英文）》 2017年第4卷第1期页码 106-115 doi: 10.15302/J-FASE-2017133

摘要： A series of dehydroabietic acid-based diarylamines have been synthesized in order to investigate their fluorescent properties, photostability, cell toxicity and fluorescence imaging. The geometries as well as their molecular properties were optimized at the B3LYP/6-31G* level using Gaussian 03. The results indicate that molecular geometry, HOMO and LUMO energies, and energy gaps are important to predict absorption and fluorescent properties. Five of the compounds can be effectively taken up by human cervical carcinoma, human hepatocellular carcinoma SMMC-7721, human gastric cancer SGC-7901 and human lung adenocarcinoma A549 cells and strong blue fluorescent signals are detected in these cells. These compounds are potential candidates for fluorescent probes in biological diagnosis.

关键词： dehydroabietic acid-based diarylamine DFT study fluorescent probe in vitro imaging

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A novel flavonol-based colorimetric and turn-on fluorescent probe for rapid determination of hydrazine

《化学科学与工程前沿（英文）》 2023年第17卷第1期页码 24-33 doi: 10.1007/s11705-022-2171-1

摘要： Hydrazine is extremely toxic and causes severe harm to human body. Herein, a novel fluorescent probe 4-oxo-2-styryl-4H-chromen-3-yl thiophene-2-carboxylate (FHT) was synthesized for detecting hydrazine by using natural cinnamaldehyde as starting material. This probe exhibited significantly enhanced fluorescence response towards hydrazine over various common metal ions, anions, and amine compounds. The detection limit of probe FHT for hydrazine was as low as 0.14 μmol·L^–1, significantly lower than that of the threshold value of 0.312 μmol·L^–1, imposed by the Environmental Protection Agency. Moreover, the proposed probe was able to detect hydrazine within wide pH (5–10) and linear detection ranges (0–110 μmol·L^–1). This probe was employed for determining trace hydrazine in different environmental water samples. The probe FHT-loaded filter paper strips were able to conveniently detect hydrazine of low concentration through distinct naked-eye and fluorescent color changes. Importantly, the probe FHT with low cytotoxicity was successfully applied to visualize hydrazine in living Hela cells and zebrafish.

关键词： cinnamaldehyde 3-hydroxychromone derivative hydrazine fluorescent probe

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Fluorescent probes and functional materials for biomedical applications

《化学科学与工程前沿（英文）》 2022年第16卷第10期页码 1425-1437 doi: 10.1007/s11705-022-2163-1

摘要： Due to their simplicity in preparation, sensitivity and selectivity, fluorescent probes have become the analytical tool of choice in a wide range of research and industrial fields, facilitating the rapid detection of chemical substances of interest as well as the study of important physiological and pathological processes at the cellular level. In addition, many long-wavelength fluorescent probes developed have also proven applicable for in vivo biomedical applications including fluorescence-guided disease diagnosis and theranostics (e.g., fluorogenic prodrugs). Impressive progresses have been made in the development of sensing agents and materials for the detection of ions, organic small molecules, and biomacromolecules including enzymes, DNAs/RNAs, lipids, and carbohydrates that play crucial roles in biological and disease-relevant events. Here, we highlight examples of fluorescent probes and functional materials for biological applications selected from the special issues “Fluorescent Probes” and “Molecular Sensors and Logic Gates” recently published in this journal, offering insights into the future development of powerful fluorescence-based chemical tools for basic biological studies and clinical translation.

关键词： fluorescent probes imaging cell biomedicine biomolecules

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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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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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A highly selective fluorescent probe for real-time imaging of UDP-glucuronosyltransferase 1A8 in living

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 103-111 doi: 10.1007/s11705-021-2064-8

摘要： Uridine diphosphate (UDP)-glucuronosyltransferases (UGTs) are enzymes involved in the biotransformation of important endogenous compounds such as steroids, bile acids, and hormones as well as exogenous substances including drugs, environmental toxicants, and carcinogens. Here, a novel fluorescent probe BDMP was developed based on boron-dipyrromethene (BODIPY) with high sensitivity for the detection of UGT1A8. The glucuronidation of BDMP not only exhibited a red-emission wavelength (λ_ex/λ_em = 500/580 nm), but also displayed an excellent UGT1A8-dependent fluorescence signal with a good linear relationship with UGT1A8 concentration. Based on this perfect biocompatibility and cell permeability, BDMP was successfully used to image endogenous UGT1A8 in human cancer cell lines (LoVo and HCT15) in real time. In addition, BDMP could also be used to visualize UGT1A8 in tumor tissues. These results suggested that BDMP is a promising molecular tool for the investigation of UGT1A8-mediated physiological function in humans.

关键词： UDP-glucuronosyltransferase 1A8 fluorescent probe subtype selectivity fluorescence imaging

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Special issue on “Fluorescent probes”

Adam C. Sedgwick, Tony D. James

《化学科学与工程前沿（英文）》 2020年第14卷第1期页码 1-3 doi: 10.1007/s11705-019-1910-4

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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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Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules

Yongqing Zhou, Xin Wang, Wei Zhang, Bo Tang, Ping Li

《化学科学与工程前沿（英文）》 2022年第16卷第1期页码 4-33 doi: 10.1007/s11705-021-2041-2

摘要： The interrelationships and synergistic regulations of bioactive molecules play pivotal roles in physiological and pathological processes involved in the initiation and development of some diseases, such as cancer and neurodegenerative and cardiovascular diseases. Therefore, the simultaneous, accurate and timely detection of two bioactive molecules is crucial to explore their roles and pathological mechanisms in related diseases. Fluorescence imaging associated with small molecular probes has been widely used in the imaging of bioactive molecules in living cells and due to its excellent performances, including high sensitivity and selectivity, noninvasive properties, real-time and high spatial temporal resolution. Single organic molecule fluorescent probes have been successively developed to simultaneously monitor two biomolecules to uncover their synergistic relationships in living systems. Hence, in this review, we focus on summarizing the design strategies, classifications, and bioimaging applications of dual-response fluorescent probes over the past decade. Furthermore, future research directions in this field are proposed.

关键词： bioactive molecules fluorescent probes in living cells and in vivo review

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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