Pharmaceutics

Editorial

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2 pages, 188 KiB

Open AccessEditorial

Biomimetic and Functional Nanomaterials for Molecular Imaging

by Pedro Ramos-Cabrer and Jesús Ruiz-Cabello

Pharmaceutics 2023, 15(6), 1570; https://doi.org/10.3390/pharmaceutics15061570 - 23 May 2023

Viewed by 1110

Abstract

Welcome to this Special Issue of the journal Pharmaceutics entitled “Biomimetic and Functional Nanomaterials for Molecular Imaging,” which focuses on the exciting advancements in molecular imaging facilitated by biomaterials and nanotechnology [...] Full article

(This article belongs to the Special Issue Biomimetic and Functional Nanomaterials for Molecular Imaging)

Research

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17 pages, 5522 KiB

Open AccessArticle

Synthetic Antiferromagnetic Gold Nanoparticles as Bimodal Contrast Agents in MRI and CT—An Experimental In Vitro and In Vivo Study

by Antoine D’Hollander, Ruben Van Roosbroeck, Jesse Trekker, Tim Stakenborg, Tom Dresselaers, Greetje Vande Velde, Tom Struys, Ivo Lambrichts, Jeroen Lammertyn, Liesbet Lagae and Uwe Himmelreich

Pharmaceutics 2021, 13(9), 1494; https://doi.org/10.3390/pharmaceutics13091494 - 17 Sep 2021

Cited by 4 | Viewed by 2299

Abstract

The use of multimodal contrast agents can potentially overcome the intrinsic limitations of individual imaging methods. We have validated synthetic antiferromagnetic nanoparticles (SAF-NPs) as bimodal contrast agents for in vitro cell labeling and in vivo cell tracking using magnetic resonance imaging (MRI) and [...] Read more.

The use of multimodal contrast agents can potentially overcome the intrinsic limitations of individual imaging methods. We have validated synthetic antiferromagnetic nanoparticles (SAF-NPs) as bimodal contrast agents for in vitro cell labeling and in vivo cell tracking using magnetic resonance imaging (MRI) and computed tomography (CT). SAF-NP-labeled cells showed high contrast in MRI phantom studies (r₂* = 712 s⁻¹ mM⁻¹), while pelleted cells showed clear contrast enhancement in CT. After intravenous SAF-NP injection, nanoparticles accumulated in the liver and spleen, as visualized in vivo by significant MRI contrast enhancement. Intravenous injection of SAF-NP-labeled cells resulted in cell accumulation in the lungs, which was clearly detectable by using CT but not by using MRI. SAF-NPs proved to be very efficient cell labeling agents for complementary MRI- and CT-based cell tracking. Bimodal monitoring of SAF-NP labeled cells is in particular of interest for applications where the applied imaging methods are not able to visualize the particles and/or cells in all organs. Full article

(This article belongs to the Special Issue Biomimetic and Functional Nanomaterials for Molecular Imaging)

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21 pages, 7820 KiB

Open AccessArticle

Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors

by Nuria Arias-Ramos, Luis Exequiel Ibarra, María Serrano-Torres, Balbino Yagüe, Matías Daniel Caverzán, Carlos Alberto Chesta, Rodrigo Emiliano Palacios and Pilar López-Larrubia

Pharmaceutics 2021, 13(8), 1258; https://doi.org/10.3390/pharmaceutics13081258 - 14 Aug 2021

Cited by 28 | Viewed by 4378

Abstract

Conjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplatforms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability in water and physiological medium. In addition, low [...] Read more.

Conjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplatforms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability in water and physiological medium. In addition, low cytotoxicity, easy functionalization, and the ability to modify CPN photochemical properties by the incorporation of dopants, convert them into excellent theranostic agents with multifunctionality for imaging and treatment. In this work, CPNs were designed and synthesized by incorporating a metal oxide magnetic core (Fe₃O₄ and NiFe₂O₄ nanoparticles, 5 nm) into their matrix during the nanoprecipitation method. This modification allowed the in vivo monitoring of nanoparticles in animal models using magnetic resonance imaging (MRI) and intravital fluorescence, techniques widely used for intracranial tumors evaluation. The modified CPNs were assessed in vivo in glioblastoma (GBM) bearing mice, both heterotopic and orthotopic developed models. Biodistribution studies were performed with MRI acquisitions and fluorescence images up to 24 h after the i.v. nanoparticles administration. The resulting IONP-doped CPNs were biocompatible in GBM tumor cells in vitro with an excellent cell incorporation depending on nanoparticle concentration exposure. IONP-doped CPNs were detected in tumor and excretory organs of the heterotopic GBM model after i.v. and i.t. injection. However, in the orthotopic GBM model, the size of the nanoparticles is probably hindering a higher effect on intratumorally T2-weighted images (T₂WI) signals and T₂ values. The photodynamic therapy (PDT)—cytotoxicity of CPNs was not either affected by the IONPs incorporation into the nanoparticles. Full article

(This article belongs to the Special Issue Biomimetic and Functional Nanomaterials for Molecular Imaging)

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12 pages, 2434 KiB

Open AccessArticle

Two in One: Use of Divalent Manganese Ions as Both Cross-Linking and MRI Contrast Agent for Intrathecal Injection of Hydrogel-Embedded Stem Cells

by Lukasz Kalkowski, Dominika Golubczyk, Joanna Kwiatkowska, Piotr Holak, Kamila Milewska, Miroslaw Janowski, Joaquim Miguel Oliveira, Piotr Walczak and Izabela Malysz-Cymborska

Pharmaceutics 2021, 13(7), 1076; https://doi.org/10.3390/pharmaceutics13071076 - 13 Jul 2021

Cited by 10 | Viewed by 3414

Abstract

Cell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in [...] Read more.

Cell therapy is a promising tool for treating central nervous system (CNS) disorders; though, the translational efforts are plagued by ineffective delivery methods. Due to the large contact surface with CNS and relatively easy access, the intrathecal route of administration is attractive in extensive or global diseases such as stroke or amyotrophic lateral sclerosis (ALS). However, the precision and efficacy of this approach are still a challenge. Hydrogels were introduced to minimize cell sedimentation and improve cell viability. At the same time, contrast agents were integrated to allow image-guided injection. Here, we report using manganese ions (Mn²⁺) as a dual agent for cross-linking alginate-based hydrogels and magnetic resonance imaging (MRI). We performed in vitro studies to test the Mn²⁺ alginate hydrogel formulations for biocompatibility, injectability, MRI signal retention time, and effect on cell viability. The selected formulation was injected intrathecally into pigs under MRI control. The biocompatibility test showed a lack of immune response, and cells suspended in the hydrogel showed greater viability than monolayer culture. Moreover, Mn²⁺-labeled hydrogel produced a strong T1 MRI signal, which enabled MRI-guided procedure. We confirmed the utility of Mn²⁺ alginate hydrogel as a carrier for cells in large animals and a contrast agent at the same time. Full article

(This article belongs to the Special Issue Biomimetic and Functional Nanomaterials for Molecular Imaging)

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13 pages, 2559 KiB

Open AccessArticle

Assessing the Potential of Molecular Imaging for Myelin Quantification in Organotypic Cultures

by Ander Egimendia, Susana Carregal-Romero, Iñaki Osorio-Querejeta, Daniel Padro, Jesús Ruiz-Cabello, David Otaegui and Pedro Ramos-Cabrer

Pharmaceutics 2021, 13(7), 975; https://doi.org/10.3390/pharmaceutics13070975 - 28 Jun 2021

Cited by 1 | Viewed by 2387

Abstract

Ex vivo models for the noninvasive study of myelin-related diseases represent an essential tool to understand the mechanisms of diseases and develop therapies against them. Herein, we assessed the potential of multimodal imaging traceable myelin-targeting liposomes to quantify myelin in organotypic cultures. Methods: [...] Read more.

Ex vivo models for the noninvasive study of myelin-related diseases represent an essential tool to understand the mechanisms of diseases and develop therapies against them. Herein, we assessed the potential of multimodal imaging traceable myelin-targeting liposomes to quantify myelin in organotypic cultures. Methods: MRI testing was used to image mouse cerebellar tissue sections and organotypic cultures. Demyelination was induced by lysolecithin treatment. Myelin-targeting liposomes were synthetized and characterized, and their capacity to quantify myelin was tested by fluorescence imaging. Results: Imaging of freshly excised tissue sections ranging from 300 µm to 1 mm in thickness was achieved with good contrast between white (WM) and gray matter (GM) using T2w MRI. The typical loss of stiffness, WM structures, and thickness of organotypic cultures required the use of diffusion-weighted methods. Designed myelin-targeting liposomes allowed for semiquantitative detection by fluorescence, but the specificity for myelin was not consistent between assays due to the unspecific binding of liposomes. Conclusions: With respect to the sensitivity, imaging of brain tissue sections and organotypic cultures by MRI is feasible, and myelin-targeting nanosystems are a promising solution to quantify myelin ex vivo. With respect to specificity, fine tuning of the probe is required. Lipid-based systems may not be suitable for this goal, due to unspecific binding to tissues. Full article

(This article belongs to the Special Issue Biomimetic and Functional Nanomaterials for Molecular Imaging)

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21 pages, 5611 KiB

Open AccessArticle

Fe₃O₄-Au Core-Shell Nanoparticles as a Multimodal Platform for In Vivo Imaging and Focused Photothermal Therapy

by Carlos Caro, Francisco Gámez, Pedro Quaresma, Jose María Páez-Muñoz, Alejandro Domínguez, John R. Pearson, Manuel Pernía Leal, Ana M. Beltrán, Yilian Fernandez-Afonso, Jesús M. De la Fuente, Ricardo Franco, Eulália Pereira and Maria Luisa García-Martín

Pharmaceutics 2021, 13(3), 416; https://doi.org/10.3390/pharmaceutics13030416 - 20 Mar 2021

Cited by 39 | Viewed by 5041

Abstract

In this study, we report the synthesis of gold-coated iron oxide nanoparticles capped with polyvinylpyrrolidone (Fe@Au NPs). The as-synthesized nanoparticles (NPs) exhibited good stability in aqueous media and excellent features as contrast agents (CA) for both magnetic resonance imaging (MRI) and X-ray computed [...] Read more.

In this study, we report the synthesis of gold-coated iron oxide nanoparticles capped with polyvinylpyrrolidone (Fe@Au NPs). The as-synthesized nanoparticles (NPs) exhibited good stability in aqueous media and excellent features as contrast agents (CA) for both magnetic resonance imaging (MRI) and X-ray computed tomography (CT). Additionally, due to the presence of the local surface plasmon resonances of gold, the NPs showed exploitable “light-to-heat” conversion ability in the near-infrared (NIR) region, a key attribute for effective photothermal therapies (PTT). In vitro experiments revealed biocompatibility as well as excellent efficiency in killing glioblastoma cells via PTT. The in vivo nontoxicity of the NPs was demonstrated using zebrafish embryos as an intermediate step between cells and rodent models. To warrant that an effective therapeutic dose was achieved inside the tumor, both intratumoral and intravenous routes were screened in rodent models by MRI and CT. The pharmacokinetics and biodistribution confirmed the multimodal imaging CA capabilities of the Fe@AuNPs and revealed constraints of the intravenous route for tumor targeting, dictating intratumoral administration for therapeutic applications. Finally, Fe@Au NPs were successfully used for an in vivo proof of concept of imaging-guided focused PTT against glioblastoma multiforme in a mouse model. Full article

(This article belongs to the Special Issue Biomimetic and Functional Nanomaterials for Molecular Imaging)

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12 pages, 3672 KiB

Open AccessArticle

Iron Oxide Nanoparticle Uptake in Mouse Brachiocephalic Artery Atherosclerotic Plaque Quantified by T₂-Mapping MRI

by Rik P. M. Moonen, Bram F. Coolen, Judith C. Sluimer, Mat J. A. P. Daemen and Gustav J. Strijkers

Pharmaceutics 2021, 13(2), 279; https://doi.org/10.3390/pharmaceutics13020279 - 19 Feb 2021

Cited by 8 | Viewed by 2499

Abstract

The purpose of our study was to monitor the iron oxide contrast agent uptake in mouse brachiocephalic artery (BCA) atherosclerotic plaques in vivo by quantitative T₂-mapping magnetic resonance imaging (MRI). Female ApoE^−/− mice (n = 32) on a 15-week [...] Read more.

The purpose of our study was to monitor the iron oxide contrast agent uptake in mouse brachiocephalic artery (BCA) atherosclerotic plaques in vivo by quantitative T₂-mapping magnetic resonance imaging (MRI). Female ApoE^−/− mice (n = 32) on a 15-week Western-type diet developed advanced plaques in the BCA and were injected with ultra-small superparamagnetic iron oxides (USPIOs). Quantitative in vivo MRI at 9.4 T was performed with a Malcolm-Levitt (MLEV) prepared T₂-mapping sequence to monitor the nanoparticle uptake in the atherosclerotic plaque. Ex vivo histology and particle electron paramagnetic resonance (pEPR) were used for validation. Longitudinal high-resolution in vivo T₂-value maps were acquired with consistent quality. Average T₂ values in the plaque decreased from a baseline value of 34.5 ± 0.6 ms to 24.0 ± 0.4 ms one day after injection and partially recovered to an average T₂ of 27 ± 0.5 ms after two days. T₂ values were inversely related to iron levels in the plaque as determined by ex vivo particle electron paramagnetic resonance (pEPR). We concluded that MRI T₂ mapping facilitates a robust quantitative readout for USPIO uptake in atherosclerotic plaques in arteries near the mouse heart. Full article

(This article belongs to the Special Issue Biomimetic and Functional Nanomaterials for Molecular Imaging)

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Review

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26 pages, 6415 KiB

Open AccessReview

New Approaches in Nanomedicine for Ischemic Stroke

by Clara Correa-Paz, Andrés da Silva-Candal, Ester Polo, Jérôme Parcq, Denis Vivien, Dusica Maysinger, Beatriz Pelaz and Francisco Campos

Pharmaceutics 2021, 13(5), 757; https://doi.org/10.3390/pharmaceutics13050757 - 20 May 2021

Cited by 20 | Viewed by 5775

Abstract

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in developed countries. Therapeutic methods such as recanalization approaches, neuroprotective drugs, or recovery strategies have been widely developed to [...] Read more.

Ischemic stroke, caused by the interruption of blood flow to the brain and subsequent neuronal death, represents one of the main causes of disability in developed countries. Therapeutic methods such as recanalization approaches, neuroprotective drugs, or recovery strategies have been widely developed to improve the patient’s outcome; however, important limitations such as a narrow therapeutic window, the ability to reach brain targets, or drug side effects constitute some of the main aspects that limit the clinical applicability of the current treatments. Nanotechnology has emerged as a promising tool to overcome many of these drug limitations and improve the efficacy of treatments for neurological diseases such as stroke. The use of nanoparticles as a contrast agent or as drug carriers to a specific target are some of the most common approaches developed in nanomedicine for stroke. Throughout this review, we have summarized our experience of using nanotechnology tools for the study of stroke and the search for novel therapies. Full article

(This article belongs to the Special Issue Biomimetic and Functional Nanomaterials for Molecular Imaging)

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