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Aims A multicentre trial, ICOS‐ONE, showed increases above the upper limit of normality of cardiac troponin (cTn) in 27% of patients within 12 months after the end of cancer chemotherapy (CT) with anthracyclines, whether cardiac protection with enalapril was started at study entry in all (prevention arm) or only upon first occurrence on supra‐normal cTn (troponin‐triggered arm). The aims of the present post hoc analysis were (i) to assess whether anthracycline‐based treatment could induce cardiotoxicity over 36 month follow‐up and (ii) to describe the time course of three cardiovascular biomarkers (i.e. troponin I cTnI‐Ultra, B‐type natriuretic peptide BNP, and pentraxin 3 PTX3) and of left ventricular (LV) function up to 36 months. Methods and results Eligible patients were those prescribed first‐in‐life CT, without evidence of cardiovascular disease, normal cTn, LV ejection fraction (EF) >50%, not on renin‐angiotensin aldosterone system antagonists. Patients underwent echocardiography and blood sampling at 24 and 36 months. No differences were observed in biomarker concentration between the two study arms, ‘prevention' vs. ‘troponin‐triggered'. During additional follow‐up 13 more deaths occurred, leading to a total of 23 (9.5%), all due to a non‐cardiovascular cause. No new occurrences of LV‐dysfunction were reported. Two additional patients were admitted to the hospital for cardiovascular causes, both for acute pulmonary embolism. No first onset of raised cTnI‐Ultra was reported in the extended follow‐up. BNP remained within normal range: at 36 months was 23.4 ng/L, higher (N.S.) than at baseline, 17.6 ng/L. PTX3 peaked at 5.2 ng/mL 1 month after CT and returned to baseline values thereafter. cTnI‐Ultra peaked at 26 ng/L 1 month after CT and returned to 3 ng/L until the last measurement at 36 months. All echocardiographic variables remained stable during follow‐up with a median LVEF of 63% and left atrial volume index about 24 mL/m2. Conclusions First‐in‐life CT with median cumulative dose of anthracyclines of 180 mg/m2 does not seem to cause clinically significant cardiac injury, as assessed by circulating biomarkers and echocardiography, in patients aged 51 years (median), without pre‐existing cardiac disease. This may suggest either a 100% efficacy of enalapril (given as preventive or troponin‐triggered) or a reassuringly low absolute cardiovascular risk in this cohort of patients, which may not require intensive cardiologic follow‐up.

Razionale. La valutazione dell’insufficienza mitralica (IM) funzionale è essenzialmente semiquantitativa ed è basata sull’angiografia o sull’ecocardiografia. La definizione di IM funzionale severa presenta difficoltà con entrambi i metodi. Nel presente lavoro sono stati presi in esame i parametri quantitativi derivati dalla valutazione dell’IM funzionale e sono stati correlati con i parametri di rimodellamento del ventricolo sinistro e dell’apparato mitralico che sono stati considerati fattori determinanti la presenza e la gravità dell’IM funzionale.Materiali e metodi. Sono stati valutati 52 pazienti con cardiomiopatia dilatativa e IM funzionale (28 maschi, 24 femmine, frazione di eiezione Risultati. I principali determinanti di ERO, VR e FR risultano la TA (beta = 0.40, 0.67 e 0.60; ES 1.68, 1.56 e 1.38; p = 0.01, p = 0.0001, p = 0.0001, rispettivamente) e MAC (beta = -0.33, -0.61, -0.61; ES 0.31, 0.31, 1.49; p = 0.03, p = 0.0001, p = 0.0001, rispettivamente). Si conferma la mancata correlazione con la frazione di eiezione. Dalla mediana dei valori ottenuti nel gruppo IM 4+ (11 pazienti) appaiono indicativi di IM funzionale severa: ERO ≥40 mm2, VR >/=49 ml/battito, FR 57%, MAC /=4.7 cm e TA >/=7.7 cm2.Conclusioni. La deformazione dell’apparato mitralico e, in particolare, TA e MAC, appaiono i principali determinanti dell’insorgenza e della gravità dell’IM funzionale. Si propongono i dati quantitativi e delle alterazioni morfo-funzionali dell’apparato mitralico indicativi di insufficienza valvolare severa.

Nanoparticles in contact with the biological environment adsorb a layer of biomolecules, which forms the biological identity of the particles. This Review outlines the concepts of the nanoparticle corona and how it interacts with biological systems, and assesses the critical problems to be resolved. The search for understanding the interactions of nanosized materials with living organisms is leading to the rapid development of key applications, including improved drug delivery by targeting nanoparticles, and resolution of the potential threat of nanotechnological devices to organisms and the environment. Unless they are specifically designed to avoid it, nanoparticles in contact with biological fluids are rapidly covered by a selected group of biomolecules to form a corona that interacts with biological systems. Here we review the basic concept of the nanoparticle corona and its structure and composition, and highlight how the properties of the corona may be linked to its biological impacts. We conclude with a critical assessment of the key problems that need to be resolved in the near future.

Cells act as extremely efficient filters for elution of unbound fluorescent tags or impurities associated with nanoparticles, including those that cannot be removed by extensive cleaning. This has consequences for quantification of nanoparticle uptake and sub-cellular localization in vitro and in vivo as a result of the presence of significant amount of labile dye even following extensive cleaning by dialysis. Polyacrylamide gel electrophoresis (PAGE) can be used to monitor the elution of unbound fluorescent probes from nanoparticles, either commercially available or synthesized in-house, and to ensure their complete purification for biological studies, including cellular uptake and sub-cellular localisation. Very different fluorescence distribution within cells is observed after short dialysis times versus following extensive dialysis against a solvent in which the free dye is more soluble, due to the contribution from free dye. In the absence of an understanding of the presence of residual free dye in (most) labeled nanoparticle solutions, the total fluorescence intensity in cells following exposure to nanoparticle solutions could be mis-ascribed to the presence of nanoparticles through the cell, rather than correctly assigned to either a combination of free-dye and nanoparticle-bound dye, or even entirely to free dye depending on the exposure conditions (i.e. aggregation of the particles etc). Where all of the dye is nanoparticle-bound, the particles are highly localized in sub-cellular organelles, likely lysosomes, whereas in a system containing significant amounts of free dye, the fluorescence is distributed through the cell due to the free diffusion of the molecule dye across all cellular barriers and into the cytoplasm.

Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases 1 , 2 . Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here, we show that the targeting ability of such functionalized nanoparticles may disappear when they are placed in a biological environment. Using transferrin-conjugated nanoparticles, we found that proteins in the media can shield transferrin from binding to both its targeted receptors on cells and soluble transferrin receptors. Although nanoparticles continue to enter cells, the targeting specificity of transferrin is lost. Our results suggest that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona 3 , 4 can ‘screen’ the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting. When placed in a complex biological environment, targeting molecules on the surface of nanoparticles are shielded by surrounding biomolecules and their ability to bind to the targeted receptors on cells is lost.

Advances in engineering functional structures at the nanoscale have led to the generation of a wide range of nanoparticles (NPs) with promising therapeutic applications. However, when NPs come into contact with a biological environment, they strongly interact with the available biomolecules, such as glycoproteins. Their adsorption on the NP’s surface forms the “ biomolecular corona”. Recent findings have shown that the glycosylation of the corona affects NPs’ stability, and it is unclear whether it can engage with receptors present in the body. By dissecting the corona’s glycan composition with enzymatic approaches, we demonstrate, through differential centrifugal sedimentation and quartz crystal microbalance, that differences in the monosaccharide sialic acid content change the NP-corona interactions with isolated glycan receptors. Furthermore, flow cytometry data confirmed this behaviour in relevant cell lines. Overall, these findings highlight the role of the biomolecular corona glycosylation in NP’s interaction, suggesting advanced parameters to predict their biological fate. Nanoparticles (NPs) hold promise for therapeutic applications, but their interactions with biological environments remain poorly understood. Here, the authors reveal that the glycosylation of the biomolecular corona, particularly sialic acid content, significantly influences NP interactions with cellular uptake processes, offering new insights into predicting NPs’ biological fate.

In this work, liposomes loaded with the fungicide, Fludioxonil (FLUD), for the containment of fungal diseases in agriculture were developed. Three types of vesicles with different compositions were compared: (I) plain vesicles, composed of soy phosphatidylcholine and cholesterol; (II) PEG-coated vesicles, with an additional polyethylene glycol coating; and (III) cationic vesicles, containing didodecyldimethylammonium bromide. Nanometric-sized vesicles were obtained both by the micelle-to-vesicle transition method and by the extrusion technique, and encapsulation efficiency, drug loading content, and Zeta potential were determined for all the samples. The extruded and PEGylated liposomes were the most stable over time and together with the cationic ones showed a significant prolonged FLUD release capacity. The liposomes’ biological activity was evaluated on conidial germination, germ tube elongation and colony radial growth of the ascomycete Botrytis cinerea, a phytopathogenic fungus affecting worldwide many important agricultural crops in the field as well as in the postharvest phase. The extruded and PEGylated liposomes showed greater effectiveness in inhibiting germ tube elongation and colony radial growth of the fungal pathogen, even at 0.01 µg·mL−1, the lowest concentration assessed.

Duchenne muscular dystrophy is a relatively common disease that affects skeletal muscle, leading to progressive paralysis and death. There is currently no resolutive therapy. We have developed a treatment in which we combined the effects of nitric oxide with nonsteroidal antiinflammatory activity by using HCT 1026, a nitric oxide-releasing derivative of flurbiprofen. Here, we report the results of long-term (1-year) oral treatment with HCT 1026 of two murine models for limb girdle and Duchenne muscular dystrophies (α-sarcoglycan-null and mdx mice). In both models, HCT 1026 significantly ameliorated the morphological, biochemical, and functional phenotype in the absence of secondary effects, efficiently slowing down disease progression. HCT 1026 acted by reducing inflammation, preventing muscle damage, and preserving the number and function of satellite cells. HCT 1026 was significantly more effective than the corticosteroid prednisolone, which was analyzed in parallel. As an additional beneficial effect, HCT 1026 enhanced the therapeutic efficacy of arterially delivered donor stem cells, by increasing 4-fold their ability to migrate and reconstitute muscle fibers. The therapeutic strategy we propose is not selective for a subset of mutations; it provides ground for immediate clinical experimentation with HCT 1026 alone, which is approved for use in humans; and it sets the stage for combined therapies with donor or autologous, genetically corrected stem cells.