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15 pages, 4060 KiB

Open AccessArticle

Exploring the Usability of α-MSH-SM-Liposome as an Imaging Agent to Study Biodegradable Bone Implants In Vivo

by Sana Riyaz, Heike Helmholz, Tuula Penate Medina, Oula Peñate Medina, Olga Will, Yu Sun, Björn Wiese, Claus-Christian Glüer and Regine Willumeit-Römer

Int. J. Mol. Sci. 2023, 24(2), 1103; https://doi.org/10.3390/ijms24021103 - 06 Jan 2023

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Abstract

Novel biodegradable metal alloys are increasingly used as implant materials. The implantation can be accompanied by an inflammatory response to a foreign object. For studying inflammation in the implantation area, non-invasive imaging methods are needed. In vivo imaging for the implanted area and [...] Read more.

Novel biodegradable metal alloys are increasingly used as implant materials. The implantation can be accompanied by an inflammatory response to a foreign object. For studying inflammation in the implantation area, non-invasive imaging methods are needed. In vivo imaging for the implanted area and its surroundings will provide beneficiary information to understand implant-related inflammation and help to monitor it. Therefore, inflammation-sensitive fluorescent liposomes in rats were tested in the presence of an implant to evaluate their usability in studying inflammation. The sphingomyelin-containing liposomes carrying alpha-melanocyte-stimulating hormone (α-MSH)-peptide were tested in a rat bone implant model. The liposome interaction with implant material (Mg-10Gd) was analyzed with Mg-based implant material (Mg-10Gd) in vitro. The liposome uptake process was studied in the bone-marrow-derived macrophages in vitro. Finally, this liposomal tracer was tested in vivo. It was found that α-MSH coupled sphingomyelin-containing liposomes and the Mg-10Gd implant did not have any disturbing influence on each other. The clearance of liposomes was observed in the presence of an inert and biodegradable implant. The degradable Mg-10Gd was used as an alloy example; however, the presented imaging system offers a new possible use of α-MSH-SM-liposomes as tools for investigating implant responses. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 3.0)

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10 pages, 479 KiB

Open AccessArticle

Functional Correlates of Striatal Dopamine Transporter Cerebrospinal Fluid Levels in Alzheimer’s Disease: A Preliminary ¹⁸F-FDG PET/CT Study

by Riccardo Camedda, Chiara Giuseppina Bonomi, Martina Gaia Di Donna and Agostino Chiaravalloti

Int. J. Mol. Sci. 2023, 24(1), 751; https://doi.org/10.3390/ijms24010751 - 01 Jan 2023

Cited by 2 | Viewed by 1809

Abstract

The aim of our study was to investigate regional glucose metabolism with 18F-FDG positron emission tomography/computed tomography in a population of patients with Alzheimer’s disease (AD) in relation to cerebrospinal (CSF) levels of striatal dopamine transporter (DAT). All patients underwent lumbar puncture and [...] Read more.

The aim of our study was to investigate regional glucose metabolism with 18F-FDG positron emission tomography/computed tomography in a population of patients with Alzheimer’s disease (AD) in relation to cerebrospinal (CSF) levels of striatal dopamine transporter (DAT). All patients underwent lumbar puncture and received a biomarker-based diagnosis of AD. Differences in regional brain glucose metabolism were assessed by Statistical Parametric Mapping version 12 with the use of age, gender, and MMSE as covariates in the analysis. A positive correlation between CSF DAT levels and glucose metabolism at the level of two brain areas involved in the pathophysiological process of Alzheimer’s disease, the substantia nigra and the posterior cingulate gyrus, has been highlighted. Results indicate that patients with higher CSF DAT levels have a better metabolic pattern in two key zones, suggesting less advanced disease status in patients with more conserved dopaminergic systems. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 3.0)

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16 pages, 3850 KiB

Open AccessArticle

Ex Vivo Evaluation of Ethosomes and Transethosomes Applied on Human Skin: A Comparative Study

by Elisabetta Esposito, Laura Calderan, Andrea Galvan, Enrica Cappellozza, Markus Drechsler, Paolo Mariani, Alessia Pepe, Maddalena Sguizzato, Enrico Vigato, Edoardo Dalla Pozza and Manuela Malatesta

Int. J. Mol. Sci. 2022, 23(23), 15112; https://doi.org/10.3390/ijms232315112 - 01 Dec 2022

Cited by 14 | Viewed by 1859

Abstract

In this study, the transdermal fate of vesicular nanosystems was investigated. Particularly, ethosomes based on phosphatidylcholine 0.9% w/w and transethosomes based on phosphatidylcholine 0.9 or 2.7% w/w plus polysorbate 80 0.3% w/w as an edge activator were [...] Read more.

In this study, the transdermal fate of vesicular nanosystems was investigated. Particularly, ethosomes based on phosphatidylcholine 0.9% w/w and transethosomes based on phosphatidylcholine 0.9 or 2.7% w/w plus polysorbate 80 0.3% w/w as an edge activator were prepared and characterized. The vesicle mean size, morphology and deformability were influenced by both phosphatidylcholine and polysorbate 80. Indeed, the mean diameters of ethosome were around 200 nm, while transethosome’s mean diameters were 146 or 350 nm in the case of phosphatidylcholine 0.9 or 2.7%, w/w, respectively. The highest deformability was achieved by transethosomes based on phosphatidylcholine 0.9%, w/w. The three types of vesicular nanosystems were applied on explanted human skin maintained in a bioreactor. Transmission electron microscopy demonstrated that all vesicles were able to enter the skin, keeping their structural integrity. Notably, the vesicle penetration capability was influenced by their physical-chemical features. Indeed, ethosomes reached keratinocytes and even the dermis, phosphatidylcholine 0.9% transethosomes were found in keratinocytes and phosphatidylcholine 2.7% transethosomes were found only in corneocytes of the outer layer. These findings open interesting perspectives for a differentiated application of these vesicles for transdermal drug delivery as a function of the cutaneous pathology to be addressed. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 3.0)

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15 pages, 2475 KiB

Open AccessArticle

Visualization of Murine Vascular Remodeling and Blood Flow Dynamics by Ultra-High-Frequency Ultrasound Imaging

by Vincent Q. Sier, Alwin de Jong, Paul H. A. Quax and Margreet R. de Vries

Int. J. Mol. Sci. 2022, 23(21), 13298; https://doi.org/10.3390/ijms232113298 - 31 Oct 2022

Viewed by 1911

Abstract

Vein grafts (VGs) are used to bypass atherosclerotic obstructions and arteriovenous fistulas (AVFs) as vascular access for hemodialysis. Vascular remodeling governs post-interventional arterialization, but may also induce VG and AVF failure. Although the endpoint characteristics of vascular remodeling are known, the in vivo [...] Read more.

Vein grafts (VGs) are used to bypass atherosclerotic obstructions and arteriovenous fistulas (AVFs) as vascular access for hemodialysis. Vascular remodeling governs post-interventional arterialization, but may also induce VG and AVF failure. Although the endpoint characteristics of vascular remodeling are known, the in vivo process and the role of blood flow dynamics has not been fully studied. Therefore, here we non-invasively quantify vascular remodeling and blood flow alterations over time in murine VG and AVF models. C57BL/6J (n = 7, chow diet) and atherosclerosis-prone ApoE3*Leiden (n = 7) mice underwent VG surgery. Ultrasound imaging was performed at 3, 7, 14, 21, and 28 days post-surgery. C57BL/6J mice (n = 8) received AVF surgery. Ultrasound imaging was performed at 7 and 14 days post-surgery. The luminal volume increased by 42% in the VGs of C57BL/6J and 38% in the VGs of ApoE3*Leiden mice at 28 days relative to 3 days post-surgery. Longitudinally, an 82% increase in wall volume and 76% increase in outward remodeling was found in the ApoE3*Leiden mice, with a constant wall size in C57BL/6J mice. Proximally, the pulsatility index, resistive index, and peak systolic velocity decreased longitudinally in both groups. Distally, the maximum acceleration increased with 56% in C57BL/6J VGs. Among the AVFs, 50% showed maturation after 7 days, based on a novel flow-criterium of 23 mL/min. Distinct flow patterns were observed at the anastomotic site and inflow artery of the AVFs relative to the control carotid arteries. Vascular remodeling can be quantified by ultra-high-frequency ultrasound imaging over time in complex animal models, via three-dimensional structural parameters and site-specific hemodynamic indices. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 3.0)

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13 pages, 2380 KiB

Open AccessArticle

Spatial Reorganization of Liquid Crystalline Domains of Red Blood Cells in Type 2 Diabetic Patients with Peripheral Artery Disease

by Giada Bianchetti, Gaetano Emanuele Rizzo, Cassandra Serantoni, Alessio Abeltino, Alessandro Rizzi, Linda Tartaglione, Salvatore Caputo, Andrea Flex, Marco De Spirito, Dario Pitocco and Giuseppe Maulucci

Int. J. Mol. Sci. 2022, 23(19), 11126; https://doi.org/10.3390/ijms231911126 - 22 Sep 2022

Cited by 3 | Viewed by 1591

Abstract

In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). [...] Read more.

In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). The contextual liquid crystalline (LC) domain spatial organization in the membrane was analysed to investigate the phase dynamics of the transition. Twenty-seven patients with long-duration T2DM were recruited and classified in DM, including 12 non-PAD patients, and DM + PAD, including 15 patients in any stage of PAD. Mean values of RBC generalized polarization (GP), representative of membrane fluidity, together with spatial organization of LC domains were compared between the two groups; p-values < 0.05 were considered statistically significant. Although comparable for anthropometric characteristics, duration of diabetes, and HbA1c, RBC membranes of PAD patients were found to be significantly more fluid (GP: 0.501 ± 0.026) than non-PAD patients (GP: 0.519 ± 0.007). These alterations were shown to be triggered by changes in both LC microdomain composition and distribution. We found a decrease in Feret diameter from 0.245 ± 0.281 μm in DM to 0.183 ± 0.124 μm in DM + PAD, and an increase in circularity. Altered RBC membrane fluidity is correlated to a spatial reconfiguration of LC domains, which, by possibly altering metabolic function, are associated with the development of T2DM-related macroangiopathic complications. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 3.0)

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20 pages, 7022 KiB

Open AccessArticle

In Vivo Two-Photon Imaging Analysis of Dynamic Degradation of Hepatic Lipid Droplets in MS-275-Treated Mouse Liver

by Chang-Gun Lee, Soo-Jin Lee, Seokho Park, Sung-E Choi, Min-Woo Song, Hyo Won Lee, Hae Jin Kim, Yup Kang, Kwan Woo Lee, Hwan Myung Kim, Jong-Young Kwak, In-Jeong Lee and Ja Young Jeon

Int. J. Mol. Sci. 2022, 23(17), 9978; https://doi.org/10.3390/ijms23179978 - 01 Sep 2022

Cited by 1 | Viewed by 2456

Abstract

The accumulation of hepatic lipid droplets (LDs) is a hallmark of non-alcoholic fatty liver disease (NAFLD). Appropriate degradation of hepatic LDs and oxidation of complete free fatty acids (FFAs) are important for preventing the development of NAFLD. Histone deacetylase (HDAC) is involved in [...] Read more.

The accumulation of hepatic lipid droplets (LDs) is a hallmark of non-alcoholic fatty liver disease (NAFLD). Appropriate degradation of hepatic LDs and oxidation of complete free fatty acids (FFAs) are important for preventing the development of NAFLD. Histone deacetylase (HDAC) is involved in the impaired lipid metabolism seen in high-fat diet (HFD)-induced obese mice. Here, we evaluated the effect of MS-275, an inhibitor of HDAC1/3, on the degradation of hepatic LDs and FFA oxidation in HFD-induced NAFLD mice. To assess the dynamic degradation of hepatic LDs and FFA oxidation in fatty livers of MS-275-treated HFD C57BL/6J mice, an intravital two-photon imaging system was used and biochemical analysis was performed. The MS-275 improved hepatic metabolic alterations in HFD-induced fatty liver by increasing the dynamic degradation of hepatic LDs and the interaction between LDs and lysozyme in the fatty liver. Numerous peri-droplet mitochondria, lipolysis, and lipophagy were observed in the MS-275-treated mouse fatty liver. Biochemical analysis revealed that the lipolysis and autophagy pathways were activated in MS-275 treated mouse liver. In addition, MS-275 reduced the de novo lipogenesis, but increased the mitochondrial oxidation and the expression levels of oxidation-related genes, such as PPARa, MCAD, CPT1b, and FGF21. Taken together, these results suggest that MS-275 stimulates the degradation of hepatic LDs and mitochondrial free fatty acid oxidation, thus protecting against HFD-induced NAFLD. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 3.0)

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16 pages, 10180 KiB

Open AccessArticle

Ligand-Specific Nano-Contrast Agents Promote Enhanced Breast Cancer CT Detection at 0.5 mg Au

by Kalyan Ramesh, Alice Truong, Yuzhen Wang, Mary Rusckowski and Manos Gkikas

Int. J. Mol. Sci. 2022, 23(17), 9926; https://doi.org/10.3390/ijms23179926 - 01 Sep 2022

Cited by 1 | Viewed by 2019

Abstract

For many cancer types, being undetectable from early symptoms or blood tests, or often detected at late stages, medical imaging emerges as the most efficient tool for cancer screening. MRI, ultrasound, X-rays (mammography), and X-ray CT (CT) are currently used in hospitals with [...] Read more.

For many cancer types, being undetectable from early symptoms or blood tests, or often detected at late stages, medical imaging emerges as the most efficient tool for cancer screening. MRI, ultrasound, X-rays (mammography), and X-ray CT (CT) are currently used in hospitals with variable costs. Diagnostic materials that can detect breast tumors through molecular recognition and amplify the signal at the targeting site in combination with state-of-the-art CT techniques, such as dual-energy CT, could lead to a more precise detection and assist significantly in image-guided intervention. Herein, we have developed a ligand-specific X-ray contrast agent that recognizes α5β1 integrins overexpressed in MDA-MB-231 breast cancer cells for detection of triple (−) cancer, which proliferates very aggressively. In vitro studies show binding and internalization of our nanoprobes within those cells, towards uncoated nanoparticles (NPs) and saline. In vivo studies show high retention of ~3 nm ligand-PEG-S-AuNPs in breast tumors in mice (up to 21 days) and pronounced CT detection, with statistical significance from saline and iohexol, though only 0.5 mg of metal were utilized. In addition, accumulation of ligand-specific NPs is shown in tumors with minimal presence in other organs, relative to controls. The prolonged, low-metal, NP-enhanced spectral-CT detection of triple (−) breast cancer could lead to breakthrough advances in X-ray cancer diagnostics, nanotechnology, and medicine. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 3.0)

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Review

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17 pages, 2431 KiB

Open AccessReview

Nanoparticle-Based Techniques for Bladder Cancer Imaging: A Review

by Federico Boschi and Manuela Malatesta

Int. J. Mol. Sci. 2023, 24(4), 3812; https://doi.org/10.3390/ijms24043812 - 14 Feb 2023

Cited by 1 | Viewed by 1631

Abstract

Bladder cancer is very common in humans and is often characterized by recurrences, compromising the patient’s quality of life with a substantial social and economic impact. Both the diagnosis and treatment of bladder cancer are problematic due to the exceptionally impermeable barrier formed [...] Read more.

Bladder cancer is very common in humans and is often characterized by recurrences, compromising the patient’s quality of life with a substantial social and economic impact. Both the diagnosis and treatment of bladder cancer are problematic due to the exceptionally impermeable barrier formed by the urothelium lining the bladder; this hinders the penetration of molecules via intravesical instillation while making it difficult to precisely label the tumor tissue for surgical resection or pharmacologic treatment. Nanotechnology has been envisaged as an opportunity to improve both the diagnostic and therapeutic approaches for bladder cancer since the nanoconstructs can cross the urothelial barrier and may be functionalized for active targeting, loaded with therapeutic agents, and visualized by different imaging techniques. In this article, we offer a selection of recent experimental applications of nanoparticle-based imaging techniques, with the aim of providing an easy and rapid technical guide for the development of nanoconstructs to specifically detect bladder cancer cells. Most of these applications are based on the well-established fluorescence imaging and magnetic resonance imaging currently used in the medical field and gave positive results on bladder cancer models in vivo, thus opening promising perspectives for the translation of preclinical results to the clinical practice. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 3.0)

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