RESUMEN

Antibodies, disruptive potent therapeutic agents against pharmacological targets, face a barrier in crossing immune systems and cellular membranes. To overcome these, various strategies have been explored including shuttling via liposomes or biocamouflaged nanoparticles. Here, we demonstrate the feasibility of loading antibodies into exosome-mimetic nanovesicles derived from human red-blood-cell membranes, which can act as nanocarriers for intracellular delivery. Goat-antichicken antibodies are loaded into erythrocyte-derived nanovesicles, and their loading yields are characterized and compared with smaller dUTP-cargo molecules. Applying dual-color coincident fluorescence burst analyses, the loading yield of nanocarriers is rigorously profiled at the single-vesicle level, overcoming challenges due to size-heterogeneity and demonstrating a maximum antibody-loading yield of 38-41% at the optimal vesicle radius of 52 nm. The achieved average loading yields, amounting to 14% across the entire nanovesicle population, with more than two antibodies per loaded vesicle, are fully comparable to those obtained for the much smaller dUTP molecules loaded in the nanovesicles after additional exosome-spin-column purification. The results suggest a promising new avenue for therapeutic delivery of antibodies, potentially encompassing also intracellular targets and suitable for large-scale pharmacological applications, which relies on the exosome-mimetic properties, biocompatibility, and low-immunogenicity of bioengineered nanocarriers synthesized from human erythrocyte membranes.

RESUMEN

The current study presents the electronic and magnetic properties of monolayer ZrSe2nanoribbons. The impact of various point defects in the form of Zr or Se vacancies, and their combinations, on the nanoribbon electronic and magnetic properties are investigated using density functional theory calculations in hydrogen-terminated zigzag and armchair ZrSe2nanoribbons. Although pristine ZrSe2is non-magnetic, all the defective ZrSe2structures exhibit ferromagnetic behavior. Our calculated results also show that the Zr and Se vacancy defects alter the total spin magnetic moment with D6Se,leading to a significant amount of 6.34µB in the zigzag nanoribbon, while the largest magnetic moment of 5.52µB is induced by D2Se-2in the armchair structure, with the spin density predominantly distributed around the Zr atoms near the defect sites. Further, the impact of defects on the performance of the ZrSe2nanoribbon-based devices is investigated. Our carrier transport calculations reveal spin-polarized current-voltage characteristics for both the zigzag and armchair devices, revealing negative differential resistance (NDR) feature. Moreover, the current level in the zigzag-based nanoribbon devices is ∼10 times higher than the armchair devices, while the peak-to-valley ratio is more pronounced in the armchair-based nanoribbon devices. It is also noted that defects increase the current level in the zigzag devices while they lead to multiple NDR peaks with rather negligible change in the current level in the armchair devices. Our results on the defective ZrSe2structures, as opposed to the pristine ones that are previously studied, provide insight into ZrSe2material and device properties as a promising nanomaterial for spintronics applications and can be considered as practical guidance to experimental work.

RESUMEN

The possible targeting functionality and low immunogenicity of exosomes and exosome-like nanovesicles make them promising as drug-delivery carriers. To tap into this potential, accurate non-destructive methods to load them and characterize their contents are of utmost importance. However, the small size, polydispersity, and aggregation of nanovesicles in solution make quantitative characterizations of their loading particularly challenging. Here, an ad-hoc methodology is developed based on burst analysis of dual-color confocal fluorescence microscopy experiments, suited for quantitative characterizations of exosome-like nanovesicles and of their fluorescently-labeled loading. It is applied to study exosome-mimetic nanovesicles derived from animal extracellular-vesicles and human red blood cell detergent-resistant membranes, loaded with fluorescently-tagged dUTP cargo molecules. For both classes of nanovesicles, successful loading is proved and by dual-color coincident fluorescence burst analysis, size statistics and loading yields are retrieved and quantified. The procedure affords single-vesicle characterizations well-suited for the investigation of a variety of cargo molecules and biological nanovesicle combinations besides the proof-of-principle demonstrations of this study. The results highlight a powerful characterization tool essential for optimizing the loading process and for advanced engineering of biomimetic nanovesicles for therapeutic drug delivery.

Asunto(s)

Exosomas , Vesículas Extracelulares , Animales , Biomimética , Sistemas de Liberación de Medicamentos/métodos , Exosomas/metabolismo , Vesículas Extracelulares/metabolismo , Fluorescencia

RESUMEN

This work is focused on the effects of doping and neutralizing edges of armchair graphene nanoribbon (AGNR) on its gas sensing behavior. Four types of structures, pristine AGNR, boron doped AGNR, nitrogen doped AGNR and defective AGNR, when the ribbons edges are terminated by both hydrogen and oxygen atoms at the same time, are investigated in detail. First, interaction of the aforementioned structures with three gases molecules, CO, O2 and CO2, are investigated by using the density functional theory, then their applications as gas sensors are studied. An AGNR structure depending on its edge termination and type of the adsorbed gas illustrates different atomic configurations. Different atomic configurations show different physical structure, chemical behavior and electronic properties. Our results have shown that the adsorptions of the three gases molecules have stronger interaction with the defective AGNR than with the other three AGNR structures. Therefore, based on quantum analysis of energy and calculation of current flow, the defective AGNR neutralized by both H and O at edges, concurrently, shows high sensitivities to CO, O2 and CO2 gases molecules. In fact, the strong interactions between adsorbed gases molecules and AGNR cause significant changes in electronic properties of edge terminated AGNR. It is worth mentioning that the sensitivity of graphene based gas sensors could be significantly improved by introducing suitable dopants and defects. The results presented in this work indicate that the defective AGNR terminated by both hydrogen and oxygen atoms can operate as a selective CO, O2 and CO2 gas sensor.