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Ashish Kumar Agrawal, Kuldeep Kumar, Nitin Kumar Swarnakar, Varun Kushwah, Sanyog Jain
In the present report we investigate the feasibility of liquid crystalline nanoparticles (LCNPs) to improve the stability and therapeutic efficacy of insulin following oral administration. Compatibility studies of different formulation ingredients with insulin and extensive optimization of different process variables resulted into the formation of LCNPs with particle size of 245.50 ± 6.36 nm, PDI 0.220 ± 0.042, zeta potential -18.30 ± 1.27 mV with an entrapment efficiency of 44.17 ± 1.47%. Mannitol (5% w/v) was identified as suitable cryoprotectant to produce freeze dried LCNPs without affecting the critical quality attributes of the LCNPs...
April 27, 2017: Molecular Pharmaceutics
Shi-Zhen Wang, Yong-Hui Zhang, Hong Ren, Ya-Li Wang, Wei Jiang, Bai-Shan Fang
Multi-enzyme complexes have the potential to achieve high catalytic efficiency for sequence reactions due to their advantages in eliminating product inhibition, facilitating intermediate transfer and in situ regenerating cofactors. Constructing functional multi-enzyme systems to mimic natural multi-enzyme complexes is of great interest for multi-enzymatic biosynthesis and cell-free synthetic biotransformation, but with many challenges. Currently, various assembly strategies have been developed based on the interaction of biomacromolecules such as DNA, peptide and scaffolding protein...
April 20, 2017: Critical Reviews in Biotechnology
Yuan Ping, Dawei Ding, Ricardo A N S Ramos, Harini Mohanram, Kanagavel Deepankumar, Jianqing Gao, Guping Tang, Ali Miserez
Suckerin proteins, recently discovered in the sucker ring teeth of squids, represent a family of promising structural biomacromolecules that can form supramolecular networks stabilized by nanoconfined β-sheets. Exploiting this feature as well as their specific amino acid composition, we demonstrate that artificial suckerin-19 (S-19) can be engineered into nanocarriers for efficient drug delivery and gene transfection in vitro and in vivo. First, we demonstrate that S-19 self-assembles into β-sheet stabilized nanoparticles with controlled particle sizes of 100-200 nm that are able to encapsulate hydrophobic drugs for pH-dependent release in vitro, and that can effectively inhibit tumor growth in vivo...
April 26, 2017: ACS Nano
Si Chen, Zhiwei Feng, Yun Wang, Shifan Ma, Ziheng Hu, Peng Yang, Yifeng Chai, Xiang-Qun Sean Xie
Tumor Necrosis Factor alpha (TNF-α) is overexpressed in various diseases, and it has been a validated therapeutic target for autoimmune diseases. All therapeutics currently used targeting TNF-α are biomacromolecules, and limited numbers of TNF-α chemical inhibitors have been reported, which makes the identification of small molecule alternatives in urgent need. Recent studies mainly focused on identifying small molecules that directly bind to TNF-α or TNF receptor-1 (TNFR1), and/or inhibit the interaction between TNF-α and TNFR1, and/or regulate related signaling pathways...
April 19, 2017: Journal of Chemical Information and Modeling
A Nolles, N J E van Dongen, A H Westphal, A J W G Visser, J M Kleijn, W J H van Berkel, J W Borst
Complex coacervate core micelles (C3Ms) are colloidal structures useful for encapsulation of biomacromolecules. We previously demonstrated that enhanced green fluorescent protein (EGFP) can be encapsulated into C3Ms using the diblock copolymer poly(2-methyl-vinyl-pyridinium)41-b-poly(ethylene-oxide)205. This packaging resulted in deviating spectroscopic features of the encapsulated EGFP molecules. Here we show that for monomeric EGFP variant (mEGFP) micellar encapsulation affects the absorption and fluorescence properties to a much lesser extent, and that changes in circular dichroism characteristics are specific for encapsulated EGFP...
April 19, 2017: Physical Chemistry Chemical Physics: PCCP
Avinash A Kadam, Jiseon Jang, Dae Sung Lee
Halloysite nanotubes (HNTs) were tuned with supermagnetic Fe3O4 (M-HNTs) and functionalized with γ-aminopropyltriethoxysilane (APTES) (A-M-HNTs). Gluteraldehyde (GTA) was linked to A-M-HNTs (A-M-HNTs-GTA) and explored for covalent laccase immobilization. The structural characterization of M-HNTs, A-M-HNTs, and A-M-HNTs-GTA-immobilized laccase (A-M-HNTs-GTA-Lac) was determined by X-ray photoelectron spectroscopy, field-emission high-resolution transmission electron microscopy, a magnetic property measurement system, and thermogavimetric analyses...
April 25, 2017: ACS Applied Materials & Interfaces
Wenxuan Cai, Trisha Tucholski, Bifan Chen, Andrew J Alpert, Sean McIlwain, Takushi Kohmoto, Song Jin, Ying Ge
Mass spectrometry (MS)-based top-down proteomics is a powerful method for the comprehensive analysis of proteoforms that arise from genetic variations and post-translational modifications (PTMs). However, top-down MS analysis of high molecular weight (MW) proteins remains challenging mainly due to the exponential decay of signal-to-noise ratio with increasing MW. Size exclusion chromatography (SEC) is a favored method for size-based separation of biomacromolecules, but typically suffers from low resolution...
April 13, 2017: Analytical Chemistry
Nina Buch-Månson, Dong-Hee Kang, Dongyoon Kim, Kyung Eun Lee, Myung-Han Yoon, Karen L Martinez
Over the past decade, vertical nanostructures have provided novel approaches for biomedical applications such as intracellular delivery/detection, specific cell capture, membrane potential measurement, and cellular activity regulation. Although the feasibility of the vertical nanostructures as a new biological tool has been thoroughly demonstrated, a better understanding of cell behavior on vertical nanostructures, in particular the effects of geometry, is essential for advanced applications. To investigate the cell behavior according to the variation of the spacing between vertical nanostructures, we have interfaced fibroblasts (NIH3T3) with density-controlled vertical silicon nanocolumn arrays (vSNAs)...
April 12, 2017: Nanoscale
Henrik Carlsson, Jenny Aasa, Natalia Kotova, Daniel Vare, Pedro F M Sousa, Per Mikael Rydberg, Lilianne Abramsson-Zetterberg, Margareta Åsa Törnqvist
Electrophilic compounds/metabolites present in humans, originating from endogenous processes or exogenous exposure, pose a risk for health effects through their reactions with nucleophilic sites in proteins and DNA, forming adducts. Adductomic approaches are developed to screen for adducts to biomacromolecules in vivo by mass spectrometry (MS), with the aim to detect adducts corresponding to unknown exposures from electrophiles. In the present study, adductomic screening was performed using blood samples from healthy children about 12 years old (n=51)...
April 11, 2017: Chemical Research in Toxicology
Yi-Yun Timothy Tsao, Karen L Wooley
A grand challenge that crosses synthetic chemistry and biology is the scalable production of functional analogues of biomacromolecules. We have focused our attention on the use of deoxynucleoside building blocks bearing non-natural bases to develop a synthetic methodology that allows for the construction of high molecular weight deoxynucleotide polymers. Our six-membered cyclic phosphoester ring-opening polymerization strategy is demonstrated, herein, by an initial preparation of novel polyphosphoesters, comprised of butenyl-functionalized deoxyribonucleoside repeat units, connected via 3',5'-backbone linkages...
April 10, 2017: Journal of the American Chemical Society
Joshua A Jackman, Abdul Rahim Ferhan, Nam-Joon Cho
In recent years, nanoplasmonic sensors have become widely used for the label-free detection of biomolecules across medical, biotechnology, and environmental science applications. To date, many nanoplasmonic sensing strategies have been developed with outstanding measurement capabilities, enabling detection down to the single-molecule level. One of the most promising directions has been surface-based nanoplasmonic sensors, and the potential of such technologies is still emerging. Going beyond detection, surface-based nanoplasmonic sensors open the door to enhanced, quantitative measurement capabilities across the biointerfacial sciences by taking advantage of high surface sensitivity that pairs well with the size of medically important biomacromolecules and biological particulates such as viruses and exosomes...
April 6, 2017: Chemical Society Reviews
Aya Umeno, Vasudevanpillai Biju, Yasukazu Yoshida
Breakthroughs in biochemistry have furthered our understanding of the onset and progression of various diseases, and have advanced the development of new therapeutics. Oxidative stress and reactive oxygen species (ROS) are ubiquitous in biological systems. ROS can be formed non-enzymatically by chemical, photochemical and electron transfer reactions, or as the byproducts of endogenous enzymatic reactions, phagocytosis, and inflammation. Imbalances in ROS homeostasis, caused by impairments in antioxidant enzymes or non-enzymatic antioxidant networks, increase oxidative stress, leading to the deleterious oxidation and chemical modification of biomacromolecules such as lipids, DNA, and proteins...
April 3, 2017: Free Radical Research
Maely P Fávero-Retto, Luiz Henrique Guerreiro, Cássio M Pessanha, Leonardo C Palmieri, Luís Maurício T R Lima
The characterization of conformational and oligomeric distribution of proteins is of paramount importance for the understanding of the correlation between structure and function. Among the bioanalytical approaches currently available, the electrospray ionization-mass spectrometry (ESI-MS) coupled to ion mobility spectrometry (IMS) is the best suited for high resolution identification with high sensitivity, allowing the in situ separation of oligomeric and conformational species. We tested the performance of the ESI-MS technique along with the IMS separation approach on a broad variety of insulin and insulin analogues with distinct oligomeric distribution pattern...
January 2017: Biologicals: Journal of the International Association of Biological Standardization
Jing Zhang, Tianqi Wang, Shengjun Mu, Livesey D Olerile, Xiaoyue Yu, Na Zhang
AIM: Hybrids composed of various materials are highly versatile for drug delivery in tumor therapy including hepatocellular carcinoma. Herein, a sorafenib (SF)-loaded biomacromolecule hyaluronic acid (HA)/lipid hybrid nanoparticles (HA/SF-cLNS) were developed for targeting drug delivery. MATERIALS & METHODS: In vitro assays determined HA/SF-cLNS release behavior, enzymatic degradation, uptake and cytotoxicity. H22-bearing liver cancer xenograft murine models were used to evaluate the biodistribution and therapeutic efficacy in vivo...
March 24, 2017: Nanomedicine
Hao Yin, Kevin J Kauffman, Daniel G Anderson
With the recent development of CRISPR technology, it is becoming increasingly easy to engineer the genome. Genome-editing systems based on CRISPR, as well as transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), are becoming valuable tools for biomedical research, drug discovery and development, and even gene therapy. However, for each of these systems to effectively enter cells of interest and perform their function, efficient and safe delivery technologies are needed. This Review discusses the principles of biomacromolecule delivery and gene editing, examines recent advances and challenges in non-viral and viral delivery methods, and highlights the status of related clinical trials...
March 24, 2017: Nature Reviews. Drug Discovery
Daheui Choi, Jaeseong Park, Jiwoong Heo, Tong In Oh, EunAh Lee, Jinkee Hong
Cell encapsulation has been reported to convey cytoprotective effects and to better maintain cell survival. In contrast to other studies, our report shows that the deposition of two major biomacromolecules, collagen type I (Col) and hyaluronic acid (HA), on mesenchymal stem cells (MSCs) does not entirely block the cell plasma membrane surface. Instead, a considerable amount of the surface remained uncovered or only slightly covered, as confirmed by TEM observation and by FACS analysis based on quantitative surface labeling...
March 28, 2017: ACS Applied Materials & Interfaces
Zacharias J Kinney, C Scott Hartley
Many foldamers, oligomers that adopt well-defined secondary structures, are now known, including many exhibiting functional behavior. However, examples of foldamer subunits within larger architectures remain rare, despite the importance of higher-order structure in biomacromolecules. Here, we investigate the dynamic covalent assembly of short o-phenylenes, a simple class of aromatic foldamers, into twisted macrocycles. o-Phenylene tetramers have been combined with rod-shaped p-phenylene-, tolane-, and diphenylbutadiyene-based linkers using imine formation...
March 27, 2017: Journal of the American Chemical Society
Conggangg Li, Jiajing Zhao, Kai Cheng, Yuwei Ge, Qiong Wu, Yansheng Ye, Guohua Xu, Zeting Zhang, Wenwen Zheng, Xu Zhang, Xin Zhou, Gary Pielak, Maili Liu
Investigating the structure, modification, interaction, and function of biomolecules in their native cellular environment leads to physiologically relevant knowledge about their mechanisms, which will benefit drug discovery and design. In recent years, nuclear and electron magnetic resonance (NMR) spectroscopy has emerged as a useful tool for elucidating the structure and function of biomacromolecules, including proteins, nucleic acids, and carbohydrates in living cells at atomic resolution. In this review, we summarize the progress and future of in-cell NMR as it is applied to proteins, nucleic acids, and carbohydrates...
March 9, 2017: Annual Review of Analytical Chemistry
Jiandong Cui, Yuxiao Feng, Tao Lin, Zhilei Tan, Cheng Zhong, Shiru Jia
Metal-organic frameworks (MOFs) have recently emerged as a promising candidates for the immobilization of enzymes due to their diversified structures and porosity. However, a lack of good size and morphological control over the as-prepared MOFs has limited their practical applications in some cases. Herein, instead of zeolitic imidazolate framework-8 (ZIF-8) with the standard rhombic dodecahedral morphology, we successfully synthesize a novel mesoporous catalase@ZIF composite with cruciate flower-like morphology by embedding catalase molecules into uniformly sized ZIF crystals...
March 29, 2017: ACS Applied Materials & Interfaces
Lu Xu, Shuli Dong, Jingcheng Hao, Jiwei Cui, Heinz Hoffmann
It is difficult to synthesize magnetic gold nanoparticles (AuNPs) with ultrafine sizes (<2 nm) based on a conventional method via coating AuNPs using magnetic particles, compounds, or ions. Here, magnetic cationic surfactants C16H33N(+)(CH3)3[CeCl3Br](-) (CTACe) and C16H33N(+)(CH3)3[GdCl3Br](-) (CTAGd) are prepared by a one-step coordination reaction, i.e., C16H33N(+)(CH3)3Br(-) (CTABr) + CeCl3 or GdCl3 → CTACe or CTAGd. A simple strategy for fabricate ultrafine (<2 nm) magnetic gold nanoparticles (AuNPs) via surface modification with weak oxidizing paramagnetic cationic surfactants, CTACe or CTAGd, is developed...
March 17, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
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