Editorial

3 pages, 166 KiB

Open AccessEditorial

Molecular Imaging in Nanomedical Research 2.0

by Manuela Malatesta

Int. J. Mol. Sci. 2022, 23(21), 13011; https://doi.org/10.3390/ijms232113011 - 27 Oct 2022

Viewed by 794

Over the last two decades, imaging techniques have become irreplaceable tools in nanotechnology: electron microscopy techniques are routinely used to observe the structural features of newly manufactured nanoconstructs, while light and electron microscopy, magnetic resonance imaging, optical imaging, positron emission tomography, and ultrasound [...] Read more.

Over the last two decades, imaging techniques have become irreplaceable tools in nanotechnology: electron microscopy techniques are routinely used to observe the structural features of newly manufactured nanoconstructs, while light and electron microscopy, magnetic resonance imaging, optical imaging, positron emission tomography, and ultrasound imaging allow dynamic monitoring of the biodistribution, targeting and clearance of nanoparticulates in living systems, either for the whole organism or at the level of single cells, tissues and organs [...] Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

Research

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17 pages, 6350 KiB

Open AccessArticle

Runx1 Messenger RNA Delivered by Polyplex Nanomicelles Alleviate Spinal Disc Hydration Loss in a Rat Disc Degeneration Model

by Cheng-Chung Chang, Hsi-Kai Tsou, Hsu-Hsin Chang, Long Yi Chan, Guan-Yu Zhuo, Tomoji Maeda and Chin-Yu Lin

Int. J. Mol. Sci. 2022, 23(1), 565; https://doi.org/10.3390/ijms23010565 - 05 Jan 2022

Cited by 13 | Viewed by 2683

Abstract

Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is [...] Read more.

Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is still controversial. One possible mechanism points to the homeostatic status of extracellular matrix (ECM) anabolism, and catabolism in the disc may play a vital role in the disease’s progression. If the damaged disc receives an abundant amount of cartilage, anabolic factors may stimulate the residual cells in the damaged disc to secrete the ECM and mitigate the degeneration process. To examine this hypothesis, a cartilage anabolic factor, Runx1, was expressed by mRNA through a sophisticated polyamine-based PEG-polyplex nanomicelle delivery system in the damaged disc in a rat model. The mRNA medicine and polyamine carrier have favorable safety characteristics and biocompatibility for regenerative medicine. The endocytosis of mRNA-loaded polyplex nanomicelles in vitro, mRNA delivery efficacy, hydration content, disc shrinkage, and ECM in the disc in vivo were also examined. The data revealed that the mRNA-loaded polyplex nanomicelle was promptly engulfed by cellular late endosome, then spread into the cytosol homogeneously at a rate of less than 20 min post-administration of the mRNA medicine. The mRNA expression persisted for at least 6-days post-injection in vivo. Furthermore, the Runx1 mRNA delivered by polyplex nanomicelles increased hydration content by ≈43% in the punctured disc at 4-weeks post-injection (wpi) compared with naked Runx1 mRNA administration. Meanwhile, the disc space and ECM production were also significantly ameliorated in the polyplex nanomicelle group. This study demonstrated that anabolic factor administration by polyplex nanomicelle-protected mRNA medicine, such as Runx1, plays a key role in alleviating the progress of DDD, which is an imbalance scenario of disc metabolism. This platform could be further developed as a promising strategy applied to regenerative medicine. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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20 pages, 4267 KiB

Open AccessArticle

Pharmacokinetics of Single Domain Antibodies and Conjugated Nanoparticles Using a Hybrid near Infrared Method

by Shiran Su, Thomas J. Esparza, Duong Nguyen, Simone Mastrogiacomo, Joong H. Kim and David L. Brody

Int. J. Mol. Sci. 2021, 22(16), 8695; https://doi.org/10.3390/ijms22168695 - 13 Aug 2021

Cited by 6 | Viewed by 2488

Abstract

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop [...] Read more.

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain were assessed by serial in vivo NIR imaging. These studies were performed under “basal” circumstances in which the VHH constructs and VHH-conjugated nanoparticles do not substantially interact with targets nor cross the blood brain barrier. Using this approach, we constructed a five-compartment PK model that fits the data well for single VHHs, engineered VHH trimers, and iron oxide nanoparticles conjugated to VHH trimers. The establishment of the feasibility of these methods lays a foundation for future PK studies of candidate brain MRI molecular contrast agents. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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19 pages, 2880 KiB

Open AccessArticle

Albumin-Coated Single-Core Iron Oxide Nanoparticles for Enhanced Molecular Magnetic Imaging (MRI/MPI)

by Abdulkader Baki, Amani Remmo, Norbert Löwa, Frank Wiekhorst and Regina Bleul

Int. J. Mol. Sci. 2021, 22(12), 6235; https://doi.org/10.3390/ijms22126235 - 09 Jun 2021

Cited by 24 | Viewed by 3923

Abstract

Colloidal stability of magnetic iron oxide nanoparticles (MNP) in physiological environments is crucial for their (bio)medical application. MNP are potential contrast agents for different imaging modalities such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Applied as a hybrid method (MRI/MPI), [...] Read more.

Colloidal stability of magnetic iron oxide nanoparticles (MNP) in physiological environments is crucial for their (bio)medical application. MNP are potential contrast agents for different imaging modalities such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Applied as a hybrid method (MRI/MPI), these are valuable tools for molecular imaging. Continuously synthesized and in-situ stabilized single-core MNP were further modified by albumin coating. Synthesizing and coating of MNP were carried out in aqueous media without using any organic solvent in a simple procedure. The additional steric stabilization with the biocompatible protein, namely bovine serum albumin (BSA), led to potential contrast agents suitable for multimodal (MRI/MPI) imaging. The colloidal stability of BSA-coated MNP was investigated in different sodium chloride concentrations (50 to 150 mM) in short- and long-term incubation (from two hours to one week) using physiochemical characterization techniques such as transmission electron microscopy (TEM) for core size and differential centrifugal sedimentation (DCS) for hydrodynamic size. Magnetic characterization such as magnetic particle spectroscopy (MPS) and nuclear magnetic resonance (NMR) measurements confirmed the successful surface modification as well as exceptional colloidal stability of the relatively large single-core MNP. For comparison, two commercially available MNP systems were investigated, MNP-clusters, the former liver contrast agent (Resovist), and single-core MNP (SHP-30) manufactured by thermal decomposition. The tailored core size, colloidal stability in a physiological environment, and magnetic performance of our MNP indicate their ability to be used as molecular magnetic contrast agents for MPI and MRI. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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Review

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35 pages, 4772 KiB

Open AccessReview

Molecular Contrast Optical Coherence Tomography and Its Applications in Medicine

by Ancong Wang, Wenliu Qi, Tianxin Gao and Xiaoying Tang

Int. J. Mol. Sci. 2022, 23(6), 3038; https://doi.org/10.3390/ijms23063038 - 11 Mar 2022

Cited by 6 | Viewed by 2926

Abstract

The growing need to understand the molecular mechanisms of diseases has prompted the revolution in molecular imaging techniques along with nanomedicine development. Conventional optical coherence tomography (OCT) is a low-cost in vivo imaging modality that provides unique high spatial and temporal resolution anatomic [...] Read more.

The growing need to understand the molecular mechanisms of diseases has prompted the revolution in molecular imaging techniques along with nanomedicine development. Conventional optical coherence tomography (OCT) is a low-cost in vivo imaging modality that provides unique high spatial and temporal resolution anatomic images but little molecular information. However, given the widespread adoption of OCT in research and clinical practice, its robust molecular imaging extensions are strongly desired to combine with anatomical images. A range of relevant approaches has been reported already. In this article, we review the recent advances of molecular contrast OCT imaging techniques, the corresponding contrast agents, especially the nanoparticle-based ones, and their applications. We also summarize the properties, design criteria, merit, and demerit of those contrast agents. In the end, the prospects and challenges for further research and development in this field are outlined. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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14 pages, 608 KiB

Open AccessReview

Molecular Imaging and Nanotechnology—Emerging Tools in Diagnostics and Therapy

by Marcin Woźniak, Agata Płoska, Anna Siekierzycka, Lawrence W. Dobrucki, Leszek Kalinowski and Iwona T. Dobrucki

Int. J. Mol. Sci. 2022, 23(5), 2658; https://doi.org/10.3390/ijms23052658 - 28 Feb 2022

Cited by 10 | Viewed by 2550

Abstract

Personalized medicine is emerging as a new goal in the diagnosis and treatment of diseases. This approach aims to establish differences between patients suffering from the same disease, which allows to choose the most effective treatment. Molecular imaging (MI) enables advanced insight into [...] Read more.

Personalized medicine is emerging as a new goal in the diagnosis and treatment of diseases. This approach aims to establish differences between patients suffering from the same disease, which allows to choose the most effective treatment. Molecular imaging (MI) enables advanced insight into molecule interactions and disease pathology, improving the process of diagnosis and therapy and, for that reason, plays a crucial role in personalized medicine. Nanoparticles are widely used in MI techniques due to their size, high surface area to volume ratio, and multifunctional properties. After conjugation to specific ligands and drugs, nanoparticles can transport therapeutic compounds directly to their area of action and therefore may be used in theranostics—the simultaneous implementation of treatment and diagnostics. This review summarizes different MI techniques, including optical imaging, ultrasound imaging, magnetic resonance imaging, nuclear imaging, and computed tomography imaging with theranostics nanoparticles. Furthermore, it explores the potential use of constructs that enables multimodal imaging and track diseases in real time. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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17 pages, 1977 KiB

Open AccessReview

Transmission Electron Microscopy as a Powerful Tool to Investigate the Interaction of Nanoparticles with Subcellular Structures

by Manuela Malatesta

Int. J. Mol. Sci. 2021, 22(23), 12789; https://doi.org/10.3390/ijms222312789 - 26 Nov 2021

Cited by 40 | Viewed by 5436

Abstract

Nanomedical research necessarily involves the study of the interactions between nanoparticulates and the biological environment. Transmission electron microscopy has proven to be a powerful tool in providing information about nanoparticle uptake, biodistribution and relationships with cell and tissue components, thanks to its high [...] Read more.

Nanomedical research necessarily involves the study of the interactions between nanoparticulates and the biological environment. Transmission electron microscopy has proven to be a powerful tool in providing information about nanoparticle uptake, biodistribution and relationships with cell and tissue components, thanks to its high resolution. This article aims to overview the transmission electron microscopy techniques used to explore the impact of nanoconstructs on biological systems, highlighting the functional value of ultrastructural morphology, histochemistry and microanalysis as well as their fundamental contribution to the advancement of nanomedicine. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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30 pages, 920 KiB

Open AccessReview

Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review

by Giovanni Palermo, Sara Giannoni, Gabriele Bellini, Gabriele Siciliano and Roberto Ceravolo

Int. J. Mol. Sci. 2021, 22(20), 11234; https://doi.org/10.3390/ijms222011234 - 18 Oct 2021

Cited by 19 | Viewed by 8970

Abstract

A major goal of current clinical research in Parkinson’s disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect [...] Read more.

A major goal of current clinical research in Parkinson’s disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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26 pages, 5957 KiB

Open AccessReview

Diagnostics and Therapeutics in Targeting HER2 Breast Cancer: A Novel Approach

by Chris Vi, Giovanni Mandarano and Sarah Shigdar

Int. J. Mol. Sci. 2021, 22(11), 6163; https://doi.org/10.3390/ijms22116163 - 07 Jun 2021

Cited by 12 | Viewed by 3495

Abstract

Breast cancer is one of the most commonly occurring cancers in women globally and is the primary cause of cancer mortality in females. BC is highly heterogeneous with various phenotypic expressions. The overexpression of HER2 is responsible for 15–30% of all invasive BC [...] Read more.

Breast cancer is one of the most commonly occurring cancers in women globally and is the primary cause of cancer mortality in females. BC is highly heterogeneous with various phenotypic expressions. The overexpression of HER2 is responsible for 15–30% of all invasive BC and is strongly associated with malignant behaviours, poor prognosis and decline in overall survival. Molecular imaging offers advantages over conventional imaging modalities, as it provides more sensitive and specific detection of tumours, as these techniques measure the biological and physiological processes at the cellular level to visualise the disease. Early detection and diagnosis of BC is crucial to improving clinical outcomes and prognosis. While HER2-specific antibodies and nanobodies may improve the sensitivity and specificity of molecular imaging, the radioisotope conjugation process may interfere with and may compromise their binding functionalities. Aptamers are single-stranded oligonucleotides capable of targeting biomarkers with remarkable binding specificity and affinity. Aptamers can be functionalised with radioisotopes without compromising target specificity. The attachment of different radioisotopes can determine the aptamer’s functionality in the treatment of HER2(+) BC. Several HER2 aptamers and investigations of them have been described and evaluated in this paper. We also provide recommendations for future studies with HER2 aptamers to target HER2(+) BC. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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17 pages, 2555 KiB

Open AccessReview

The Design of Abnormal Microenvironment Responsive MRI Nanoprobe and Its Application

by Ancong Wang, Xiao Han, Wenliu Qi, Sihui Du, Zhenqi Jiang and Xiaoying Tang

Int. J. Mol. Sci. 2021, 22(10), 5147; https://doi.org/10.3390/ijms22105147 - 13 May 2021

Cited by 4 | Viewed by 2512

Abstract

Magnetic resonance imaging (MRI) is often used to diagnose diseases due to its high spatial, temporal and soft tissue resolution. Frequently, probes or contrast agents are used to enhance the contrast in MRI to improve diagnostic accuracy. With the development of molecular imaging [...] Read more.

Magnetic resonance imaging (MRI) is often used to diagnose diseases due to its high spatial, temporal and soft tissue resolution. Frequently, probes or contrast agents are used to enhance the contrast in MRI to improve diagnostic accuracy. With the development of molecular imaging techniques, molecular MRI can be used to obtain 3D anatomical structure, physiology, pathology, and other relevant information regarding the lesion, which can provide an important reference for the accurate diagnosis and treatment of the disease in the early stages. Among existing contrast agents, smart or activatable nanoprobes can respond to selective stimuli, such as proving the presence of acidic pH, active enzymes, or reducing environments. The recently developed environment-responsive or smart MRI nanoprobes can specifically target cells based on differences in the cellular environment and improve the contrast between diseased tissues and normal tissues. Here, we review the design and application of these environment-responsive MRI nanoprobes. Full article

(This article belongs to the Special Issue Molecular Imaging in Nanomedical Research 2.0)

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