Editorial

2 pages, 182 KiB

Open AccessEditorial

Molecular Imaging in Nanomedical Research

by Manuela Malatesta

Int. J. Mol. Sci. 2022, 23(8), 4207; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084207 - 11 Apr 2022

Cited by 1 | Viewed by 1072

For years, nanomedical research has represented a challenge and an opportunity in terms of imaging techniques [...] Full article

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

Research

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20 pages, 4059 KiB

Open AccessArticle

Formulative Study and Intracellular Fate Evaluation of Ethosomes and Transethosomes for Vitamin D3 Delivery

by Manuela Costanzo, Elisabetta Esposito, Maddalena Sguizzato, Maria Assunta Lacavalla, Markus Drechsler, Giuseppe Valacchi, Carlo Zancanaro and Manuela Malatesta

Int. J. Mol. Sci. 2021, 22(10), 5341; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22105341 - 19 May 2021

Cited by 23 | Viewed by 2531

Abstract

In this pilot study, ethosomes and transethosomes were investigated as potential delivery systems for cholecalciferol (vitamin D3), whose deficiency has been correlated to many disorders such as dermatological diseases, systemic infections, cancer and sarcopenia. A formulative study on the influence of pharmaceutically acceptable [...] Read more.

In this pilot study, ethosomes and transethosomes were investigated as potential delivery systems for cholecalciferol (vitamin D3), whose deficiency has been correlated to many disorders such as dermatological diseases, systemic infections, cancer and sarcopenia. A formulative study on the influence of pharmaceutically acceptable ionic and non-ionic surfactants allowed the preparation of different transethosomes. In vitro cytotoxicity was evaluated in different cell types representative of epithelial, connective and muscle tissue. Then, the selected nanocarriers were further investigated at light and transmission electron microscopy to evaluate their uptake and intracellular fate. Both ethosomes and transethosomes proven to have physicochemical properties optimal for transdermal penetration and efficient vitamin D3 loading; moreover, nanocarriers were easily internalized by all cell types, although they followed distinct intracellular fates: ethosomes persisted for long times inside the cytoplasm, without inducing subcellular alteration, while transethosomes underwent rapid degradation giving rise to an intracellular accumulation of lipids. These basic results provide a solid scientific background to in vivo investigations aimed at exploring the efficacy of vitamin D3 transdermal administration in different experimental and pathological conditions. Full article

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

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13 pages, 3557 KiB

Open AccessArticle

Intraperitoneal Glucose Transport to Micrometastasis: A Multimodal In Vivo Imaging Investigation in a Mouse Lymphoma Model

by Zsombor Ritter, Katalin Zámbó, Xinkai Jia, Dávid Szöllősi, Dániel Dezső, Hussain Alizadeh, Ildikó Horváth, Nikolett Hegedűs, David Tuch, Kunal Vyas, Péter Balogh, Domokos Máthé and Erzsébet Schmidt

Int. J. Mol. Sci. 2021, 22(9), 4431; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094431 - 23 Apr 2021

Cited by 1 | Viewed by 2191

Abstract

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes. We aimed to investigate its early stage spread at one day post-intraperitoneal inoculation [...] Read more.

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes. We aimed to investigate its early stage spread at one day post-intraperitoneal inoculation of lymphoma cells (n = 18 mice), and its advanced stage at seven days post-inoculation with in vivo [18F]FDG-PET and [18F]PET/MRI, and ex vivo by autoradiography and Cherenkov luminescence imaging (CLI). Of the early stage group, nine animals received intraperitoneal injections, and nine received intravenous [18F]FDG injections. The advanced stage group (n = 3) received intravenous FDG injections. In the early stage, using autoradiography we observed a marked accumulation in the mesentery after intraperitoneal FDG injection. Using other imaging methods and autoradiography, following the intravenous injection of FDG no accumulations were detected. At the advanced stage, tracer accumulation was clearly detected in mesenteric lymph nodes and in the peritoneum after intravenous administration using PET. We confirmed the results with immunohistochemistry. Our results in this model highlight the importance of local FDG administration during diagnostic imaging to precisely assess early peritoneal manifestations of other malignancies (colon, stomach, ovary). These findings also support the importance of applying topical therapies, in addition to systemic treatments in peritoneal cancer spread. Full article

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

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17 pages, 3706 KiB

Open AccessArticle

Investigation of the Membrane Fluidity Regulation of Fatty Acid Intracellular Distribution by Fluorescence Lifetime Imaging of Novel Polarity Sensitive Fluorescent Derivatives

by Giada Bianchetti, Salome Azoulay-Ginsburg, Nimrod Yosef Keshet-Levy, Aviv Malka, Sofia Zilber, Edward E. Korshin, Shlomo Sasson, Marco De Spirito, Arie Gruzman and Giuseppe Maulucci

Int. J. Mol. Sci. 2021, 22(6), 3106; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063106 - 18 Mar 2021

Cited by 12 | Viewed by 2526

Abstract

Free fatty acids are essential structural components of the cell, and their intracellular distribution and effects on membrane organelles have crucial roles in regulating the metabolism, development, and cell cycle of most cell types. Here we engineered novel fluorescent, polarity-sensitive fatty acid derivatives, [...] Read more.

Free fatty acids are essential structural components of the cell, and their intracellular distribution and effects on membrane organelles have crucial roles in regulating the metabolism, development, and cell cycle of most cell types. Here we engineered novel fluorescent, polarity-sensitive fatty acid derivatives, with the fatty acid aliphatic chain of increasing length (from 12 to 18 carbons). As in the laurdan probe, the lipophilic acyl tail is connected to the environmentally sensitive dimethylaminonaphthalene moiety. The fluorescence lifetime imaging analysis allowed us to monitor the intracellular distribution of the free fatty acids within the cell, and to simultaneously examine how the fluidity and the microviscosity of the membrane environment influence their localization. Each of these probes can thus be used to investigate the membrane fluidity regulation of the correspondent fatty acid intracellular distribution. We observed that, in PC-12 cells, fluorescent sensitive fatty acid derivatives with increased chain length compartmentalize more preferentially in the fluid regions, characterized by a low microviscosity. Moreover, fatty acid derivatives with the longest chain compartmentalize in lipid droplets and lysosomes with characteristic lifetimes, thus making these probes a promising tool for monitoring lipophagy and related events. Full article

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

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12 pages, 2537 KiB

Open AccessArticle

An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [¹¹C]PBR28 and [¹⁸F]flumazenil PET Imaging

by Krishna Kanta Ghosh, Parasuraman Padmanabhan, Chang-Tong Yang, Zhimin Wang, Mathangi Palanivel, Kian Chye Ng, Jia Lu, Jan Carlstedt-Duke, Christer Halldin and Balázs Gulyás

Int. J. Mol. Sci. 2021, 22(2), 951; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020951 - 19 Jan 2021

Cited by 7 | Viewed by 2706

Abstract

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron [...] Read more.

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI. The present study aims to investigate whether the two radioligands, [¹¹C]PBR28 and [¹⁸F]flumazenil, are able to accurately quantify in vivo molecular-cellular changes in a rodent TBI-model for two different biochemical targets of the processes. In addition, it serves to observe any palpable variations associated with primary and secondary injury sites, and in the affected versus the contralateral hemispheres. As [¹¹C]PBR28 is a radioligand of the 18 kD translocator protein, the up-regulation of which is coupled to the level of neuroinflammation in the brain, and [¹⁸F]flumazenil is a radioligand for GABA_A-benzodiazepine receptors, whose level mirrors interneuronal activity and eventually cell death, the use of the two radioligands may reveal two critical features of TBI. An up-regulation in the [¹¹C]PBR28 uptake triggered by the LFP in the injured (right) hemisphere was noted on day 14, while the uptake of [¹⁸F]flumazenil was down-regulated on day 14. When comparing the left (contralateral) and right (LFPI) hemispheres, the differences between the two in neuroinflammation were obvious. Our results demonstrate a potential way to measure the molecular alterations in a rodent-based TBI model using PET imaging with [¹¹C]PBR28 and [¹⁸F]flumazenil. These radioligands are promising options that can be eventually used in exploring the complex in vivo pharmacokinetics and delivery mechanisms of nanoparticles in TBI treatment. Full article

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

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15 pages, 9465 KiB

Open AccessArticle

Identification of Lymphatic and Hematogenous Routes of Rapidly Labeled Radioactive and Fluorescent Exosomes through Highly Sensitive Multimodal Imaging

by Kyung Oh Jung, Young-Hwa Kim, Seock-Jin Chung, Chul-Hee Lee, Siyeon Rhee, Guillem Pratx, June-Key Chung and Hyewon Youn

Int. J. Mol. Sci. 2020, 21(21), 7850; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217850 - 22 Oct 2020

Cited by 33 | Viewed by 3385

Abstract

There has been considerable interest in the clinical use of exosomes as delivery vehicles for treatments as well as for promising diagnostic biomarkers, but the physiological distribution of exosomes must be further elucidated to validate their efficacy and safety. Here, we aimed to [...] Read more.

There has been considerable interest in the clinical use of exosomes as delivery vehicles for treatments as well as for promising diagnostic biomarkers, but the physiological distribution of exosomes must be further elucidated to validate their efficacy and safety. Here, we aimed to develop novel methods to monitor exosome biodistribution in vivo using positron emission tomography (PET) and optical imaging. Exosomes were isolated from cultured mouse breast cancer cells and labeled for PET and optical imaging. In mice, radiolabeled and fluorescently labeled exosomes were injected both via lymphatic and hematogenous metastatic routes. PET and fluorescence images were obtained and quantified. Radioactivity and fluorescence intensity of ex vivo organs were measured. PET signals from exosomes in the lymphatic metastatic route were observed in the draining sentinel lymph nodes. Immunohistochemistry revealed greater exosome uptake in brachial and axillary versus inguinal lymph nodes. Following administration through the hematogenous metastasis pathway, accumulation of exosomes was clearly observed in the lungs, liver, and spleen. Exosomes from tumor cells were successfully labeled with ⁶⁴Cu (or ⁶⁸Ga) and fluorescence and were visualized via PET and optical imaging, suggesting that this simultaneous and rapid labeling method could provide valuable information for further exosome translational research and clinical applications. Full article

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

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Review

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26 pages, 1048 KiB

Open AccessReview

Cell-Based Tracers as Trojan Horses for Image-Guided Surgery

by Vincent Q. Sier, Margreet R. de Vries, Joost R. van der Vorst, Alexander L. Vahrmeijer, Cornelis van Kooten, Luis J. Cruz, Lioe-Fee de Geus-Oei, Valerie Ferreira, Cornelis F. M. Sier, Frauke Alves and Munitta Muthana

Int. J. Mol. Sci. 2021, 22(2), 755; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020755 - 13 Jan 2021

Cited by 10 | Viewed by 4579

Abstract

Surgeons rely almost completely on their own vision and palpation to recognize affected tissues during surgery. Consequently, they are often unable to distinguish between different cells and tissue types. This makes accurate and complete resection cumbersome. Targeted image-guided surgery (IGS) provides a solution [...] Read more.

Surgeons rely almost completely on their own vision and palpation to recognize affected tissues during surgery. Consequently, they are often unable to distinguish between different cells and tissue types. This makes accurate and complete resection cumbersome. Targeted image-guided surgery (IGS) provides a solution by enabling real-time tissue recognition. Most current targeting agents (tracers) consist of antibodies or peptides equipped with a radiolabel for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), magnetic resonance imaging (MRI) labels, or a near-infrared fluorescent (NIRF) dye. These tracers are preoperatively administered to patients, home in on targeted cells or tissues, and are visualized in the operating room via dedicated imaging systems. Instead of using these ‘passive’ tracers, there are other, more ‘active’ approaches of probe delivery conceivable by using living cells (macrophages/monocytes, neutrophils, T cells, mesenchymal stromal cells), cell(-derived) fragments (platelets, extracellular vesicles (exosomes)), and microorganisms (bacteria, viruses) or, alternatively, ‘humanized’ nanoparticles. Compared with current tracers, these active contrast agents might be more efficient for the specific targeting of tumors or other pathological tissues (e.g., atherosclerotic plaques). This review provides an overview of the arsenal of possibilities applicable for the concept of cell-based tracers for IGS. Full article

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

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13 pages, 783 KiB

Open AccessReview

In Vivo Tracking of Extracellular Vesicles by Nuclear Imaging: Advances in Radiolabeling Strategies

by Sara Almeida, Liliana Santos, Amílcar Falcão, Célia Gomes and Antero Abrunhosa

Int. J. Mol. Sci. 2020, 21(24), 9443; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249443 - 11 Dec 2020

Cited by 18 | Viewed by 2772

Abstract

Extracellular vesicles (EVs) are naturally secreted vesicles that have attracted a large amount of interest in nanomedicine in recent years due to their innate biocompatibility, high stability, low immunogenicity, and important role in cell-to-cell communication during pathological processes. Their versatile nature holds great [...] Read more.

Extracellular vesicles (EVs) are naturally secreted vesicles that have attracted a large amount of interest in nanomedicine in recent years due to their innate biocompatibility, high stability, low immunogenicity, and important role in cell-to-cell communication during pathological processes. Their versatile nature holds great potential to improve the treatment of several diseases through their use as imaging biomarkers, therapeutic agents, and drug-delivery vehicles. However, the clinical translation of EV-based approaches requires a better understanding of their in vivo behavior. Several imaging technologies have been used for the non-invasive in vivo tracking of EVs, with a particular emphasis on nuclear imaging due to its high sensitivity, unlimited penetration depth and accurate quantification. In this article, we will review the biological function and inherent characteristics of EVs and provide an overview of molecular imaging modalities used for their in vivo monitoring, with a special focus on nuclear imaging. The advantages of radionuclide-based imaging modalities make them a promising tool to validate the use of EVs in the clinical setting, as they have the potential to characterize in vivo the pharmacokinetics and biological behavior of the vesicles. Furthermore, we will discuss the current methods available for radiolabeling EVs, such as covalent binding, encapsulation or intraluminal labeling and membrane radiolabeling, reporting the advantages and drawbacks of each radiolabeling approach. Full article

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

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