Precise assembly of inside-out cell membrane camouflaged nanoparticles via bioorthogonal reactions for improving drug leads capturing

Cell membrane camouflaged nanoparticles have been widely used in the field of drug leads discovery attribute to their unique biointerface targeting function. However, random orientation of cell membrane coating does not guarantee effective and appropriate binding of drugs to specific sites, especially when applied to intracellular regions of transmembrane proteins. Bioorthogonal reactions have been rapidly developed as a specific and reliable method for cell membrane functionalization without disturbing living biosystem. Herein, inside-out cell membrane camouflaged magnetic nanoparticles (IOCMMNPs) were accurately constructed via bioorthogonal reactions to screen small molecule inhibitors targeting intracellular tyrosine kinase domain of vascular endothelial growth factor recptor-2. Azide functionalized cell membrane acted as a platform for specific covalently coupling with alkynyl functionalized magnetic Fe3O4 nanoparticles to prepare IOCMMNPs. The inside-out orientation of cell membrane was successfully verified by immunogold staining and sialic acid quantification assay. Ultimately, two compounds, senkyunolide A and ligustilidel, were successfully captured, and their potential antiproliferative activities were further testified by pharmacological experiments. It is anticipated that the proposed inside-out cell membrane coating strategy endows tremendous versatility for engineering cell membrane camouflaged nanoparticles and promotes the development of drug leads discovery platforms.

Surgical management of abdominal tuberculosis in a tertiary care referral center

Background: Abdominal tuberculosis encompasses gastrointestinal, visceral and peritoneal forms of tuberculosis in different proportions. Their clinical presentation and radiological findings are varied and non-specific often warranting surgical intervention either for confirmation of diagnosis or for definitive management.  It is not very clear as of now as to which type of patients would require surgical intervention for diagnosis or treatment of abdominal tuberculosis. This study aims to profile such patients accurately to revalidate the need for surgical intervention in cases of abdominal tuberculosis.Methods: This study is a retrospective descriptive observational study wherein the documents of patients whose final diagnosis was confirmed as ‘Abdominal Tuberculosis’ from January 2011 to December 2013 were analysed. Their demographic and clinical profile, hematological, biochemical and radiological investigations including barium meal follow-through, ultrasonography, CT scan abdomen, colonoscopy and biopsy, HIV status and ascitic fluid analysis were analysed. Patients in whom diagnosis was not confirmed by these investigations, and therefore underwent diagnostic laparoscopy or exploratory laparotomy were studied. Simultaneously, patients in whom, the diagnosis was confirmed, but still underwent surgical intervention for therapeutic purposes were also analysed.Results: It was found that 44 out of 54 patients (81.4%) underwent surgical procedure.  28 (52%) required surgical intervention for confirmation of diagnosis (diagnostic procedures: diagnostic laparoscopy- 21 and exploratory laparotomy- 07) while 16 (29.4%) required therapeutic procedures (emergency- 08; elective- 08).Conclusions: In spite of extensive investigations, many patients of abdominal tuberculosis require surgical management either minimally invasive or otherwise, both for confirmation of diagnosis and for definitive management.

Nanodiamonds with powerful ability for drug delivery and biomedical applications: Recent updates on in vivo study and patents / 药物分析学报

Nanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical, chemical, optical and biological properties, making them significant active moiety carriers for biomedical application. These are known as the most'captivating' crystals attributed to their chemical inertness and unique properties posing them useful for variety of applications in biomedical era. Alongside, it becomes increasingly important to find, ascertain and circumvent the negative aspects associated with nano-diamonds. Surface modification or functionalization with biological molecules plays a significant role in managing the toxic behavior since nanodiamonds have tailorable surface chemistry. To take advantage of nanodiamond potential in drug delivery, focus has to be laid on its purity, surface chemistry and other considerations which may directly or indirectly affect drug adsorption on nanodiamond and drug release in biological environment. This review emphasizes on the basic properties, synthesis techniques, surface modification techniques, toxicity issues and biomedical applications of nanodiamonds. For the devel-opment of nanodiamonds as an effective dosage form, researchers are still engaged in the in-depth study of nanodiamonds and their effect on life interfaces.

Uso de Biomateriales Funcionalizados con Moléculas Bioactivas en la Ingeniería Biomédica / Use of Functionalized Biomaterials with Bioactive molecules in Biomedical Engineering

Resumen El artículo expone la importancia del uso de moléculas bioactivas para la funcionalización de biomateriales. Por esta razón, se realizó una revisión de investigaciones actuales y relevantes en diversos buscadores de datos, incluyendo los diferentes tipos de materiales y moléculas bioactivas utilizadas para elaborar biomateriales funcionalizados, con énfasis en los procesos y sus propiedades. Se encontró que el proceso de funcionalización o modificación de la superficie expande el camino para adaptar al biomaterial de acuerdo al entorno fisiológico de las células vivas. De esta manera, el proceso mejora la estructura y las funciones de los tejidos y órganos diseñados. Existen una variedad de métodos y moléculas bioactivas disponibles para la funcionalización de los biomateriales, las cuales dependen de la manera en las que las células o tejidos se regeneran. Entre los diferentes materiales para la fabricación de biomateriales, las biomoléculas como las proteínas, lípidos, carbohidratos, entre otros, son una de las opciones más utilizadas debido a la similitud de estas con los sistemas biológicos del cuerpo humano. Finalmente, el artículo también integra algunas de las más prometedoras aplicaciones de moléculas bioactivas incorporadas a los biomateriales.

Abstract The paper exposes the importance of the use of bioactive molecules for the functionalization of biomaterials. For this reason, a review of current and relevant research was carried out in various data searchers, including the different types of bioactive materials and molecules used to elaborate functionalized biomaterials, with emphasis on the processes and their properties. It was found that the process of functionalization or modification of the surface expands the path to adapt the biomaterial according to the physiological environment of living cells. This process improves the structure and functions of the designed tissues and organs. There are a variety of methods and bioactive molecules available for the functionalization of biomaterials, depending on the way in which the cells or tissues are regenerated. Among the different materials for the manufacture of biomaterials, biomolecules such as proteins, lipids, carbohydrates, among others, are one of the most used options due to the similarity of these with the biological systems of the human body. Finally, the paper also integrates some of the most promising applications of bioactive molecules incorporated into biomaterials.

Advanced applications of membrane technology in biological detection / 生物工程学报

Membrane creates the functions of protection, supporting, dispersion and separation. More functions can be designed by modifying membrane surface and grafting/loading selective ligands or catalysts on the membrane, thus membrane technology has been widely applied in biological detection, and its application approaches becomes diverse. Rational design of functional membranes can meet the demands in different steps of biological detection process, including sample pretreatment, preparation, response and sensing. This review summarized the functionalization methods of filtration membranes, applications of membrane technology in sample preparation and detection process, as well as the research on the integration of functional membranes. By revisiting the research progress on functional membrane design, preparation and applications for biological detection, it is expected to take better advantage of membrane materials structure and performance for constructing efficient and stable detection platform, which is more "adapted" to the detection environment.

Functionalized genetic engineered silk-based biomaterials and their applications / 生物工程学报

Silk-based biomaterials are featured with excellent mechanical properties, good biocompatibility and biodegradability, which contribute to their potential applications in biomedical field. The current recognition of silk protein materials in structure and function provides a basic theory for the transformation of silk protein into new types of biomaterials. In addition, exogenous sequences encoding new peptide or structural domain can be inserted into the maternal gene sequences encoding silk proteins through genetic engineering technology to synthesize novel silk-based biomaterials with unique functions. This review summarizes the current trend and development perspective of genetically engineered functional silk-based materials for biomedical applications.

Click-Functionalized Fluorescent Nanoprobes with Folate Receptor-Targeting Ability for Cancer Cell Imaging / 分析化学

Folate receptor ( FR )-targeted fluorescent nanoprobes ( RSiNPs-Folate ) were constructed by modifying Rubpy-doped silica nanoparticles ( RSiNPs) with folic acid ( FA) based on click chemistry coupling method, which was successfully used for cancer cell imaging. Firstly, RSiNPs were prepared by St?ber method and modified with azide groups through the hydrolysis of silane coupling agents ( Az-PTES ) , then propargyl folate were conjugated onto the nanoparticle surfaces via click reaction. It was demonstrated that the FA-functionalized nanoprobes were successfully prepared by monitoring the characteristic peak of the azide group at 2105 cm-1 before and after coupling. In the condition of physiological pH, the nanoprobes exhibited strong red emission at 601 nm when excited at the 458 nm excitation wavelength. The cell imaging results showed that RSiNPs-Folate could effectively target FR-positive HeLa cells, while no obvious fluorescence was observed for FR-negative A549 cells. The receptor-mediated imaging mechanism was confirmed by free FA competition experiments. More importantly, HeLa cells could be selectively recognized and imaged in the mixing cell system. Compared with the carbodiimide conjugation protocols, the click-functionalized nanoprobes had many advantages such as simple synthesis procedures, mild reaction conditions and high yields, which could be potentially used for fluorescent labeling and imaging of different cancer cells.

Effects of functionalization of multi-walled carbon nanotubes on human peripheral blood mononuclear cell / 国际生物医学工程杂志

Objective To explore the effects of surface functionalized multi-walled carbon nanotubes (FMWCNTs) on the cytotoxicity of human peripheral blood mononuclear cell (PBMC).Methods Five different types of MWCNTs (hydroxylated,carboxylated,aminated,nickel-plated and pristine MWCNTs (P-MWCNTs)) with the same diameter and length were evaluated the dispersion and characterizations in physiological salt solution by transmission electron microscopy.PBMC were isolated by density gradient centrifugation from human peripheral blood,and 5 types of MWCNTs were ultrasonically dispersed in serum-containing medium respectively.After incubation with PBMC for 12,24,48 or 72 h,cytotoxicity was detected by CCK-8 kits.Results All the MWCNTs had well dispersion,especially the F-MWCNTs.Cytotoxicity results showed that all types of MWCNTs could induced PBMC death,and presented dose-dependence manner and a certain degree of time-dependence manner.Compared with the P-MWCNTs,F-MWCNTs changed cytotoxicity statistically,with the hydroxylated,carboxylated,aminated MWCNTs weakened,aminated MWCNTs significant (P＜0.05),nevertheless the nickel-plated MWCNTs increased.Compared with the P-MWCNTs (25 μg/ml),cell viability of PBMC after 24 and 48 h incubation with the same dose of nickelplated MWCNTs both decreased,and the differences was statistically significant (P＜0.01,P＜0.05).Conclusions The functional group modification affects not only the MWCNTs dispersion in medium,but also the cytotoxicity of the MWCNTs on PBMC.

Synthesis and Applications of Gold Nanoparticle Probes / 分析化学

During last decade, gold nanoparticled (AuNPs)-based assays have been well-developed and widely used in biological analysis and biomedical detection because AuNPs have unique physical and chemical properties which depend on the size, shape and degree of aggregation.The AuNPs-based assays have already been employed for detecting practical samples with high simplicity and selectivity.This review discusses the recently development of the synthesis and biological molecular functionalisation of AuNPs and their applications on the heavy metallic cations, small organic compounds, nucleic acids and proteins detection and cellular analysis.

Antimaláricos: construcción de híbridos moleculares de la cloroquina: [revisión] / Antimalarials: construction of molecular hybrids based on chloroquine: [review]

La resistencia desarrollada por el Plasmodium falciparum ante los fármacos tradicionales del tipo 4-amino-7-cloroquinolínicos ha llevado al diseño y síntesis de inhibidores duales, como los híbridos de la cloroquina. Además del farmacóforo típico en esta clase de antimaláricos, tales híbridos incorporan un espaciador metilénico como parte de un fragmento diamínico, cuyo propósito es la funcionalización del grupo amino terminal en sistemas heterocíclicos diversos con actividades biológicas reportadas. Esto con el fin de evitar la rápida e liminación de la molécula por parte del parásito, lo que se conoce como resistencia. Se discuten el diseño y síntesis de estos híbridos moleculares.

The resistance developed by Plasmodium falciparum againsttraditional 4-amino-7-chloroquinolinic drugs has lead to the design and synthesis of dual inhibitors such as chloroquine hybrids. Besides the usual pharmacophore in this type of antimalarials, such hybrids incorporate a methylenic spacer as part of a diaminic fragment whose purpose is the functionalization of the terminal amino group in various heterocyclic systems having reported biological activities. The prime goal is to avoid the molecule rapid elimination by the parasite, which is known as resistance. The design and synthesis of these molecular hybrids are discussed.

A resistência desenvolvida pelo Plasmodium falciparum frente aos fármacos tradicionais do tipo 4-amino-7-cloroquinolínicos tem levado ao desenho e síntese de inibidores duais, como os híbridos da cloroquina. Além do farmacóforo típico nesta classe de antimaláricos, tais híbridos incorporam um espaçador metilénico como parte de um fragmento diamínico, que tem por propósito a funcionalização do grupo amino terminal em sistemas heterocíclicos diversos com atividadesbiológicas reportadas. Isto com a finalidade de evitar a rápida eliminação da molécula por parte do parasito, o que se conhece como resistência. É discutido o desenho e sínteses destes híbridos moleculares.

Development of Macrocyclic Ligands for Stable Radiometal Complexes / 대한핵의학회잡지

Current interest in the regioselective N-functionalization of tetraazacycloalkanes (cyclen and cyclam) stems mainly from their complexes with radioactive metals for applications in diagnostic (64Cu, 111In, 67Ga) and therapeutic (90Y) medicine, and with paramagnetic ions for magnetic resonance imaging (Gd+3). Selective methods for the N-substitution of cyclen and cyclam is a crucial step in most syntheses of cyclen and cyclam-based radiometal complexes and bifunctional chelating agents. In addition, mixing different pendent groups to give hetero-substituted cyclen derivatives would be advantageous in many applications for fine-tuning the compound's physical properties. So far, numerous approaches for the regioselective N-substitution of tetraazacycloalkanes and more specifically cyclen and cyclam are reported. Unfortunately, none of them are general and every strategy has its own strong points and drawbacks. Herein, we categorize numerous regioselective N-alkylation methods into three strategies, such as 1) direct substitution of the macrocycle, 2) introduction of the functional groups prior to cyclization, and 3) protection/functionalization/deprotection. Our discussion is also split into the methods of mono- and tri-functionalization and di-functionalizataion based on number of substituents. At the end, we describe new trials for the new macrocycles which form more stable metal complexes with various radiometals, and briefly mention the commercially available tetraazacycloalkanes which are used for the biconjugation of biomolecules.