Biology subjects

Spano, R.

Publications and source records attributed to Spano, R..

3 recordsLinked to original sources

bioRxiv2026

ENHANCING TUMOR PERFUSION AND NANOMEDICINE DELIVERY VIA ENDOGENOUS NITRIC OXIDE RELEASE BY METHYL PALMITATE NANOPARTICLES

Despite a few clinical successes, the efficacy of cancer nanomedicines remains limited by rapid clearance by the mononuclear phagocytic system and poor permeation across the abnormal tumor vasculature. We previously showed that methyl palmitate nanoparticles (MPN) can safely and reversibly inhibit the phagocytic activity of immune cells for several hours, thereby improving tumor accumulation and the efficacy of systemically administered nanomedicines. Here, we demonstrate that, on a shorter time scale, MPN can induce vasodilation, introducing an additional mechanism to enhance the accumulation of therapeutic agents within the malignant tissue. Upon internalization by macrophages and endothelial cells, MPN trigger the release of endogenous nitric oxide (NO), a key mediator of vasodilation, in a concentration-, and time-dependent manner. Following MPN administration, raster-scanning optoacoustic mesoscopy (RSOM) revealed vasodilation across multiple tissues, with the strongest effect observed in tumors. To assess enhanced tumor accumulation, we injected 70 kDa fluorescent dextran and demonstrated via histology a markedly increased fluorescence signal exclusively in MPN-treated tumors compared to controls 24 hours later. In addition, positron emission tomography (PET) imaging of 89Zr-labeled clinical iron oxide nanoparticles (Feraheme) showed significantly greater tumor accumulation after a 15-minute MPN pretreatment. Finally, general serum biochemistry panels and histological analyses of major organs in healthy mice revealed no toxicity following either single or repeated MPN dosing. Overall, this study demonstrates that MPN-induced vasodilation occurring within minutes enhances intra-tumoral deposition of macromolecules and small nanoparticles. Together with their longer-term effects on phagocytosis inhibition, these findings indicate that MPN can improve therapeutic delivery through complementary, time-dependent mechanisms that increase tumor perfusion and vascular permeability.

bioengineering↗

bioRxiv2025

MEP-independent silent periods in hand muscles elicited by Transcranial Magnetic Stimulation of the ventral premotor cortex: a non-invasive tool to explore premotor negative motor areas

ObjectiveWe investigate the possibility to disrupt motor activity via premotor and parietal cortex stimulation, by inducing cortical silent periods (cSPs) in the voluntarily activated upper limb. MethodsWe analyzed data from 17 subjects with normal brain function, using navigated TMS (nTMS) on individual MR anatomies. We applied single-pulse biphasic stimulation at 120% of resting motor threshold (rMT) in blocks of 30 stimulations on each spot of a 10-16 point grid covering the inferior parietal and frontal lobes in the dominant hemisphere while participants performed voluntary submaximal contraction. Electromyography (EMG) was recorded bilaterally from intrinsic hand muscles. ResultsWe observed cSPs not preceded by a MEP in the contralateral hand in 16/17 participants. The maximum overlap, of individual areas where such MEP-independent cSPs could be evoked, corresponded to the ventral precentral gyrus (MNI coordinates: [x=-57, y=7, z=33]). In a subset of stimulus sites, MEP-independent cSPs were bilateral, with contralateral predominance. Canonical short-latency MEPs were observed in all patients, with maximum overlap over the primary motor cortex. We also observed rare contralateral long-latency (> 23 ms) MEP-like responses from peri-Rolandic TMS. ConclusionsMEP-independent cSPs are systematically elicitable in healthy participants They likely reflect interference with premotor representations of ongoing movements. They offer a novel possibility to investigate higher-order motor functions in the experimental and clinical neurosciences.

neuroscience↗

bioRxiv2025

On the biodegradation of micropatterned polymeric film

AO_SCPLOWBSTRACTC_SCPLOWPolymeric implants for local drug delivery offer significant advantages for treating various medical conditions by enabling the temporal and spatial control of drug release, improving efficacy, and reducing systemic side effects. In this context, {micro}MESH, a 20 m thin, dual-compartmentalized film comprising a poly(lactic-co-glycolic acid) (PLGA) micronetwork intercalated with a polyvinyl alcohol (PVA) microlayer, represents an interesting opportunity as its geometry can be systematically and accurately micropatterned during the fabrication process, enabling the systematic analysis of the effect of geometry on biodegradation rates mechanisms. In this study, four different {micro}MESH films were realized with different surface area-to-volume ratios (Sa/V), ranging from 0.67 to 1.7 {micro}m-1. After characterizing the {micro}MESH geometry via fluorescent and scanning electron microscopy, biodegradations studies were performed up to 60 days in different media to assess the mass loss of PLGA, the reduction in PLGA molecular weight, and the formation of macroscopic defects - pores, holes and crack - within the PLGA micronetwork. By comparing the four {micro}MESH films among themselves and to a flat, continuous PLGA slab (FLAT), it was confirmed the importance of the surface-to-volume ratio and demonstrated that {micro}MESH with higher Sa/V ratios exhibited slower degradation rates compared to FLAT. Scanning electron microscopy images of the PLGA micronetworks revealed morphological changes indicative of bulk erosion, including surface roughening and pore formation, in FLAT and {micro}MESH configurations with low Sa/V ratios. These findings confirm that film micropatterning significantly influences degradation kinetics.

bioengineering↗