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Exploiting the chirality of nanometric structures to modulate biological systems is an emerging and compelling area of research. In this study, we reveal that chiral polyurea nanocapsules exhibit significant stereoselective interactions with albumins from various sources despite their nearly neutral surface potential. Moreover, these interactions can be modulated by altering the nanocapsule surface composition, offering new opportunities to impact their distribution and, if used as a drug delivery system, the pharmacokinetics of the drug. Notably, these interactions promote preferential cellular internalization of only one chiral configuration. We synthesized chiral polyurea nanocapsules with reproducible sizes via interfacial polymerization between toluene 2,4-diisocyanate and d- or l-lysine enantiomers on a volatile oil-in-water emulsion interface, followed by solvent evaporation. Further synthesis optimization reduced the capsule size to a range compatible with in vivo administration, and capsules with alternating chiral patterns were also produced. The stereoselective interactions with albumins were assessed through capsule size changes, fluorescence quenching, and surface charge measurements. Biocompatibility, stability, and cellular internalization were evaluated. Additionally, scanning transmission electron and atomic force microscopy were carried out to assess the capsule shape, surface composition, and morphology. We discovered that d-nanocapsules exhibited 2.1-2.6 times greater albumin adsorption compared with their l-counterparts. This difference is attributed to the distinct morphology of d-nanocapsules, characterized by a more concave shape, central depression, and rougher surface. The extent of adsorption could be finely tuned by adjusting the d- and l-lysine monomer ratios during synthesis. Both chiral configurations demonstrated biocompatibility and stability with d-nanocapsules showing a 2.5-fold increase in cellular internalization.

Objectives: Adipose tissue radiodensity in computed tomography (CT) performed before surgeries can predict surgical difficulty. Despite its clinical importance, little is known about what influences radiodensity. This study combines desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and electrospray ionization (ESI) with machine learning to unveil how chemical composition of adipose tissue determines its radiodensity., Methods: Patients in the study underwent abdominal surgeries. Before surgery, CT radiodensity of fat near operated sites was measured. Fifty-three fat samples were collected and analyzed by DESI-MSI, ESI, and histology, and then sorted by radiodensity, demographic parameters, and adipocyte size. A non-negative matrix factorization (NMF) algorithm was developed to differentiate between high and low radiodensities., Results: No associations between radiodensity and patient age, gender, weight, height, or fat origin were found. Body mass index showed negative correlation with radiodensity. A substantial difference in chemical composition between adipose tissues of high and low radiodensities was observed. More radiodense tissues exhibited greater abundance of high molecular weight species, such as phospholipids of various types, ceramides, cholesterol esters and diglycerides, and about 70% smaller adipocyte size. Less radiodense tissue showed high abundance of short acyl-tail fatty acids., Conclusions: This study unveils the connection between abdominal adipose tissue radiodensity and its chemical composition. Because the radiodensity of the fat around the surgical site is associated with surgical difficulty, it is important to understand how adipose tissue composition affects this parameter. We conclude that fat tissue with a higher content of various phospholipids and waxy lipids is more CT radiodense., Clinical Relevance Statement: This study establishes the connection between the CT radiodensity of adipose tissue and its chemical composition. Clinicians may use this information for preoperative planning of surgical procedures, potentially modifying their surgical approach (for example, performing partial nephrectomy openly rather than laparoscopically)., Key Points: • Adipose tissue radiodensity values in computed tomography images taken prior to the surgery can potentially predict surgery difficulty. • Fifty-three human specimens were analyzed by advanced mass spectrometry, molecular imaging, and machine learning to establish the key features that determine Hounsfield units' values of adipose tissue. • The findings of this research will enable clinicians to better prepare for surgical procedures and select operative strategies., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Nose-to-brain delivery presents an attractive administration route for neuroactive drugs that suffer from compromised bioavailability or fail to pass the blood-brain barrier. However, the conventional gauge of effectiveness for intranasal delivery platforms primarily involves detecting the presence of the administered drug within the brain, with little insight into its precise localization within brain structures. This may undermine the therapeutic efficacy of drugs and hinder the design of systems that target specific brain regions. In this study, we designed two intranasal delivery systems for the antipsychotic drug, olanzapine, and evaluated its distribution in the rat brain following intranasal administration. The first evaluated system was an olanzapine-loaded microemulsion and the second one was nanoparticulate aqueous dispersion of olanzapine. Both systems exhibited characteristics that render them compatible for intranasal administration, and successfully delivered olanzapine to the brain. We further employed an ambient mass spectrometry imaging method, called desorption electrospray ionization mass spectrometry imaging, to visualize the signal intensity of olanzapine in different brain regions following the intranasal administration of these two systems. Substantial variations in the distribution patterns of olanzapine across various brain structures were revealed, potentially highlighting the importance of mass spectrometry imaging in designing and evaluating intranasal drug delivery platforms., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Katherine Margulis reports financial support was provided by Israel Science Foundation. Katherine Margulis reports financial support was provided by US Israel Binational Science Foundation. Katherine Margulis reports financial support was provided by Israel Cancer Research Fund. Katherine Margulis reports financial support was provided by Ministry of Science and Technology of Israel. Katherine Margulis reports financial support was provided by Council for Higher Education. Katherine Margulis reports financial support was provided by The Wolfson Foundation and the Wolfson Foundation Charity Trust. Katherine Margulis reports financial support was provided by Hebrew University of Jerusalem The David R Bloom Center for Pharmacy. Katherine Margulis reports financial support was provided by The Alex Grass Center.]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) is one of the least specimen destructive ambient ionization mass spectrometry tissue imaging methods. It enables rapid simultaneous mapping, measurement, and identification of hundreds of molecules from an unmodified tissue sample. Over the years, since its first introduction as an imaging technique in 2005, DESI-MSI has been extensively developed as a tool for separating tissue regions of various histopathologic classes for diagnostic applications. Recently, DESI-MSI has also emerged as a versatile technique that enables drug discovery and can guide the efficient development of drug delivery systems. For example, it has been increasingly employed for uncovering unique patterns of in vivo drug distribution, the discovery of potentially treatable biochemical pathways, revealing novel druggable targets, predicting therapeutic sensitivity of diseased tissues, and identifying early tissue response to pharmacological treatment. These and other recent advances in implementing DESI-MSI as the tool for the development of novel therapies are highlighted in this review., (© 2021 John Wiley & Sons Ltd.)

(1) Background: Chiral nanoparticular systems have recently emerged as a compelling platform for investigating stereospecific behavior at the nanoscopic level. We describe chiroselective supramolecular interactions that occur between DNA oligonucleotides and chiral polyurea nanocapsules. (2) Methods: We employ interfacial polyaddition reactions between toluene 2,4-diisocyanate and lysine enantiomers that occur in volatile oil-in-water nanoemulsions to synthesize hollow, solvent-free capsules with average sizes of approximately 300 nm and neutral surface potential. (3) Results: The resultant nanocapsules exhibit chiroptical activity and interact differentially with single stranded DNA oligonucleotides despite the lack of surface charge and, thus, the absence of significant electrostatic interactions. Preferential binding of DNA on D-polyurea nanocapsules compared to their L-counterparts is demonstrated by a fourfold increase in capsule size, a 50% higher rise in the absolute value of negative zeta potential (ζ-potential), and a three times lower free DNA concentration after equilibration with the excess of DNA. (4) Conclusions: We infer that the chirality of the novel polymeric nanocapsules affects their supramolecular interactions with DNA, possibly through modification of the surface morphology. These interactions can be exploited when developing carriers for gene therapy and theranostics. The resultant constructs are expected to be highly biocompatible due to their neutral potential and biodegradability of polyurea shells.

Cu 2+ -ion-modified graphene oxide nanoparticles, Cu 2+ -GO NPs, act as a heterogeneous catalyst mimicking functions of horseradish peroxidase, HRP, and of NADH peroxidase. The Cu 2+ -GO NPs catalyze the oxidation of dopamine to aminochrome by H 2 O 2 and catalyze the generation of chemiluminescence in the presence of luminol and H 2 O 2 . The Cu 2+ -GO NPs provide an active material for the chemiluminescence detection of H 2 O 2 and allow the probing of the activity of H 2 O 2 -generating oxidases and the detection of their substrates. This is exemplified with detecting glucose by the aerobic oxidation of glucose by glucose oxidase and the Cu 2+ -GO NP-stimulated chemiluminescence intensity generated by the H 2 O 2 product. Similarly, the Cu 2+ -GO NPs catalyze the H 2 O 2 oxidation of NADH to the biologically active NAD + cofactor. This catalytic system allows its conjugation to biocatalytic transformations involving NAD + -dependent enzyme, as exemplified for the alcohol dehydrogenase-catalyzed oxidation of benzyl alcohol to benzoic acid through the Cu 2+ -GO NPs-catalyzed regeneration of NAD + .