Enhanced antibacterial activity of bovine milk exosome-based drug formulation against bacterial pathogens.

Milk is not only a source of nutrients, but also contains exosomes (Exo) that can serve as a vehicle for drug delivery. Here, we obtained bovine milk Exo using three efficient methods, demonstrating high quality for commercial production. The optimized Exo displayed a size of 105.2 nm and an entrapment efficiency of 88.4 %. The Exo has been functionalized with a combination therapy comprising isobavachalcone (IS) and polymyxin B (PB), referred to as IP-Exo. The antibacterial efficacy of IP-Exo was significantly enhanced, enabling the elimination of 99 % of multidrug-resistant (MDR) bacterial pathogens in 4 h. Furthermore, scanning electron microscopy images demonstrated that the drug combination led to the complete dismantling of the bacterial structure. IP-Exo showed nearly 100 % microbial inhibition in fresh orange juice and accelerated wound healing in mouse models. Collectively, IP-Exo provides excellent potential for application within the food industry and animal husbandry as a defense against bacterial pathogens.

Milk Extracellular Vesicles: Natural Nanoparticles for Enhancing Oral Drug Delivery against Bacterial Infections.

Oral drug delivery is typically preferred as a therapeutic intervention due to the complexities and expenses associated with intravenous administration. However, some drugs are poorly absorbed orally, requiring intravenous administration to bypass the gastrointestinal tract and deliver the drug directly into the bloodstream. Thus, there is an urgent need to develop novel drug delivery platforms to overcome the challenges of oral drug delivery with low solubility, low permeability, oral degradation, and low bioavailability. Advances in extracellular vesicles (EVs) as natural carriers have provided emerging approaches to improve potential therapeutic applications. Milk not only contains traditional nutrients but is also rich in EVs. In this Review, we focus mainly on the purification of milk EVs (mEVs), their safety, and the advantages of mEV-based drug carriers in combatting intestinal infections. Additionally, we summarize several advantages of mEVs over conventional synthetic carriers, such as low immunogenicity, high biocompatibility, and the ability to transfer bioactive molecules between cells. Considering the unmet gaps of mEVs in clinical translation, it is essential to review the cargo loading into mEVs and future perspectives for their use as natural drug carriers for oral delivery. This overview of mEV-based drug carriers for oral delivery sheds light on alternative approaches to treat clinical infections associated with intestinal pathogens and the development of novel oral delivery systems.

Aptamer based label free thrombin assay based on the use of silver nanoparticles incorporated into self-polymerized dopamine.

The authors describe an electrochemical aptasensor for thrombin that is based on the use of a glassy carbon electrode (GCE) modified with polydopamine that is loaded with silver nanoparticles (PDA/AgNPs). The use of AgNPs improves the conductivity of the film and increases the surface area of the GCE. PDA was deposited on the GCE via self-polymerization, and the thrombin binding aptamer was grafted onto the PDA-modified GCE by a single step reaction. Residual electrode surface was blocked with 6-mercapto-1-hexanol. On exposure to thrombin, the electrochemical impedance of the modified electrode increases gradually. Response is linear in the 0.1 pM to 5.0 nM thrombin concentration range, and the limit of detection is as low as 36 fM. The method is selective and capable of detecting thrombin in diluted human serum. In our perception, such a GCE modified with AgNP in a PDA matrix may be applied to many other analytes for which appropriate aptamers are available. Graphical abstract Schematic of an electrochemical aptasensor for sensitive and selective thrombin detection based on the use of a self-polymerized polydopamine film loaded with silver nanoparticles.

Antifouling aptasensor for the detection of adenosine triphosphate in biological media based on mixed self-assembled aptamer and zwitterionic peptide.

Direct detection of targets in complex biological media with conventional biosensors is an enormous challenge due to the nonspecific adsorption and severe biofouling. In this work, a facile strategy for sensitive and low fouling detection of adenosine triphosphate (ATP) is developed through the construction of a mixed self-assembled biosensing interface, which was composed of zwitterionic peptide (antifouling material) and ATP aptamer (bio-recognition element). The peptide and aptamer (both containing thiol groups) were simultaneously self-assembled onto gold electrode surface electrodeposited with gold nanoparticles. The developed aptasensor possessed high selectivity and sensitivity for ATP, and it showed a wide linear response range towards ATP from 0.1pM to 5nM. Owing to the presence of peptide with excellent antifouling property in the biosensing interface, the aptasensor can detect ATP in complex biological media with remarkably reduced biofouling or nonspecific adsorption effect. Moreover, it can directly detect ATP in 1% human whole blood without suffering from any significant interference, indicating its great potential for practical assaying of ATP in biological samples.

Mixed Self-Assembly of Polyethylene Glycol and Aptamer on Polydopamine Surface for Highly Sensitive and Low-Fouling Detection of Adenosine Triphosphate in Complex Media.

Detection of disease biomarkers within complex biological media is a substantial outstanding challenge because of severe biofouling and nonspecific adsorptions. Herein, a reliable strategy for sensitive and low-fouling detection of a biomarker, adenosine triphosphate (ATP) in biological samples was developed through the formation of a mixed self-assembled sensing interface, which was constructed by simultaneously self-assembling polyethylene glycol (PEG) and ATP aptamer onto the self-polymerized polydopamine-modified electrode surface. The developed aptasensor exhibited high selectivity and sensitivity toward the detection of ATP, and the linear range was 0.1-1000 pM, with a detection limit down to 0.1 pM. Moreover, owing to the presence of PEG within the sensing interface, the aptasensor was capable of sensing ATP in complex biological media such as human plasma with significantly reduced nonspecific adsorption effect. Assaying ATP in real biological samples including breast cancer cell lysates further proved the feasibility of this biosensor for practical application.

Fabrication of AlGaN nanorods with different Al compositions for emission enhancement in UV range.

Highly ordered AlxGa1-xN nanorods with varied aluminum alloy compositions (0.18 ≤ x ≤ 0.8) are fabricated with nanoimprint lithography and top-down dry etching techniques. And the structural properties and morphology are obtained by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Compared with as-grown AlGaN samples, nanorod samples reveal outstanding optical performance on account of strain releasing and light extraction enhancement. Through Raman scattering and cathodeluminescence measurements, it has been observed clear red-shifts of E2h modes and near band edge emission (NBE) peaks of AlGaN nanorods compared to the planar ones, indicating the residual strain releasing after nano-fabrication. The integrated intensities of NBE peaks of AlGaN nanorods manifest light emission enhancement up to 2.7 at deep-UV range. Finite-difference time-domain (FDTD) simulations have been adopted to investigate the light extraction and far-field distribution of such structures, it turned out that ordered nanorod array can enhance the TM polarized emission extraction 2-7 folds compared to the planar structure. The optical regulation in nanorod arrays should take the responsibility for the observed optical enhancements, which is proved by the far-field distribution of light, thus it can improve the performance of ultraviolet LEDs.