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In a context of drug repurposing, pentamidine (PTM), an FDA-approved antiparasitic drug, has been proposed to reverse the splicing defects associated in myotonic dystrophy type 1 (DM1). However, clinical use of PTM is hinder by substantial toxicity, leading to find alternative delivery strategies. In this work we proposed hyaluronic acid-based nanoparticles as a novel encapsulation strategy to efficiently deliver PTM to skeletal muscles cells. In vitro studies on C2C12 myoblasts and myotubes showed an efficient nanoparticles' internalization with minimal toxicity. More interestingly, our findings evidenced for the first time the endosomal escape of hyaluronic acid-based nanocarriers. Ex vivo studies showed an efficient nanoparticles' internalization within skeletal muscle fibers. Finally, the therapeutic efficacy of PTM-loaded nanosystems to reduce the number of nuclear foci has been demonstrated in a novel DM1 in vitro model. So far, current data demonstrated the potency of hyaluronic acid-based nanosystems as efficient nanocarrier for delivering PTM into skeletal muscle and mitigate DM1 pathology., (Copyright © 2022 Elsevier Inc. All rights reserved.)

During last years, evidence has been provided on the involvement of overweight and obesity in the pathogenesis and aggravation of several life-threatening diseases. Here, we demonstrate that, under appropriate administration conditions, polyhedral iron oxide nanoparticles are efficiently and safely taken up by 3T3 cell line-derived adipocytes (3T3 adipocytes) in vitro. Since these nanoparticles proved to effectively produce heat when subjected to alternating magnetic field, 3T3 adipocytes were submitted to superparamagnetic iron oxide nanoparticles-mediated hyperthermia treatment (SMHT), with the aim of modulating their lipid content. Notably, the treatment resulted in a significant delipidation persisting for at least 24h, and in the absence of cell death, damage or dedifferentiation. Interestingly, transcript expression of adipose triglyceride lipase (ATGL), a key gene involved in canonical lipolysis, was not modulated upon SMHT, suggesting the involvement of a novel/alternative mechanism in the effective lipolysis observed. By applying the same experimental conditions successfully used for 3T3 adipocytes, SMHT was able to induce delipidation also in primary cultures of human adipose-derived adult stem cells. The success of this pioneering approach in vitro opens promising perspectives for the application of SMHT in vivo as an innovative safe and physiologically mild strategy against obesity, potentially useful in association with balanced diet and healthy lifestyle., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Object: Pancreatic cancer is one of the most lethal human cancer and appropriate experimental tumor models are needed for the development of innovative therapeutic approaches. This paper describes an experimental model of human pancreatic cancer and a related non invasive imaging technique suitable for monitoring tumor growth and metastatization. The aim of the work was the implementation of an experimental platform suitable for assessing the efficacy of new therapeutic agents., Materials and Methods: Human pancreatic cancer cells (PANC-1-Luc+) were injected into the pancreas of female athymic CD1 mice. Magnetic Resonance Imaging (MRI) at 4.7T and Bioluminescence Imaging (BLI) were performed in each mouse at three time points after cell inoculation (1, 2 and 3months). Two groups of mice were studied: the first group of n=13 mice in which 5*10(6) cells were injected and the second group of n=10 mice in which 2*10(6) cells were injected. MRI examination included T2w acquisitions and (at the last time point) Dynamic-contrast-enhanced-MRI (DCE-MRI)., Results: Each mouse underwent three longitudinal MRI and BLI examinations. BLI was more sensitive than MRI producing higher detection rate at early time points. Moreover in one case of abdominal dissemination of pancreatic tumor cells, small tumoral masses were detected by BLI and not detected by MRI. However BLI appears more prone to experimental error most likely due to photon attenuation. In 4 mice BLI produced false negative results. DCE-MRI experiments providing information on tumor perfusion were conducted successfully in this anatomical district and demonstrated that the tumor tissues from the second experimental group are more vascularized compared to the first group., Conclusion: The present study performed on the experimental model of pancreatic cancer here described shows that MRI and BLI are complementary techniques and that synergistic application of both can overcome the intrinsic limitations of each., (Copyright © 2015. Published by Elsevier Inc.)

Contrast-enhanced ultrasound (CEUS) is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 microm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes.