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Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy

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A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 31968

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Prof. Dr. Pablo Botella

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Instituto de Tecnología Química, Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas, Valencia, Spain
Interests: nanomedicine; drug delivery; gene delivery; targeted delivery; stimuli-responsive; controlled release; bioimaging; theranostics

Prof. Dr. Christopher C. Landry

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Department of Chemistry, University of Vermont, Burlington, USA
Interests: Christopher Landry is Chair of the Department of Chemistry at the University of Vermont. Over the past 22 years as an independent faculty member, he has studied the applications of porous nanoparticles in catalysis and biomedicine. He has prepared novel transition metal oxides for photocatalysis of organic compounds, and his research group has developed nanoparticle-based systems using tethered enzymes for simultaneous sensing and decontamination of organophosphorus toxins. In addition to designing in vivo drug delivery systems, including materials for simultaneous diagnosis and treatment of disease, his interests in biomedicine include fundamental studies on the adsorption and exchange of proteins at nanoparticle surfaces in biological media

Special Issue Information

Dear Colleagues,

It is more than two decades since the first nanomedicines were released on the market. During this time, a wide range of materials and compositions have been tested, mostly at the preclinical stage. The focus of these studies has been to address key clinical goals, such as the early diagnosis of degenerative diseases and the selective treatment of target cells or tissues. Currently, a new generation of imaging agents and nanomaterial-based pharmaceuticals are being developed, with improved biocompatibility, pharmacokinetics, and diagnostic and therapeutic efficacies. Once bioavailability limitations and regulatory matters concerning their somewhat complex compositions are addressed, rapid commercialization of these products is expected.

In this context, this Special Issue focuses on the development of novel nanoplatforms with applications in bioimaging (e.g., MRI, PET, HIFU), and/or suitable to promote selective therapies (then, minimizing side effects) through targeted delivery and specific intracellular drug release mechanisms. Manuscripts at both the preclinical and clinical levels are encouraged.

Prof. Dr. Pablo Botella
Prof. Dr. Christopher C. Landry
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

nanomedicine
bioimaging
selective therapy
targeted delivery
theranostics
stimuli-responsive
intracellular release

Published Papers (10 papers)

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Research

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14 pages, 6460 KiB

Open AccessArticle

Evaluation and Optimization of Poly-d-Lysine as a Non-Natural Cationic Polypeptide for Gene Transfer in Neuroblastoma Cells

by Miguel Sanchez-Martos, Gema Martinez-Navarrete, Adela Bernabeu-Zornoza, Lawrence Humphreys and Eduardo Fernandez

Nanomaterials 2021, 11(7), 1756; https://doi.org/10.3390/nano11071756 - 5 Jul 2021

Cited by 2 | Viewed by 2601

Abstract

Cationic polypeptides and cationic polymers have cell-penetrating capacities and have been used in gene transfer studies. In this study, we investigate the capability of a polymer of d-lysine (PDL), a chiral form of α–Poly-lysine, as a possible nonviral vector for releasing genetic materials to neuroblastoma cells and evaluate its stability against proteases. We tested and compared its transfection effectiveness in vitro as a vehicle for the EGFP plasmid DNA (pDNA) reporter in the SH-SY5Y human neuroblastoma, HeLa, and 3T3 cell lines. Using fluorescent microscopy and flow cytometry, we demonstrated high transfection efficiencies based on EGFP fluorescence in SH-SY5Y cells, compared with HeLa and 3T3. Our results reveal PDL as an efficient vector for gene delivery specifically in the SH-SY5Y cell line and suggest that PDL can be used as a synthetic cell-penetrating polypeptide for gene therapy in neuroblastoma cells. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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19 pages, 3398 KiB

Open AccessArticle

Synthesis and Characterization of a “Clickable” PBR28 TSPO-Selective Ligand Derivative Suitable for the Functionalization of Biodegradable Polymer Nanoparticles

by Renato Auriemma, Mattia Sponchioni, Umberto Capasso Palmiero, Giacomo Rossino, Arianna Rossetti, Andrea Marsala, Simona Collina, Alessandro Sacchetti, Davide Moscatelli and Marco Peviani

Nanomaterials 2021, 11(7), 1693; https://doi.org/10.3390/nano11071693 - 28 Jun 2021

Cited by 4 | Viewed by 2538

Abstract

Reactive microgliosis is a pathological hallmark that accompanies neuronal demise in many neurodegenerative diseases, ranging from acute brain/spinal cord injuries to chronic diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD) and age-related dementia. One strategy to assess and monitor microgliosis is to use positron emission tomography (PET) by exploiting radioligands selective for the 18 kDa translocator protein (TSPO) which is highly upregulated in the brain in pathological conditions. Several TSPO ligands have been developed and validated, so far. Among these, PBR28 has been widely adopted for PET imaging at both preclinical and clinical levels, thanks to its high brain penetration and high selectivity. For this reason, PBR28 represents a good candidate for functionalization strategies, where this ligand could be exploited to drive selective targeting of TSPO-expressing cells. Since the PBR28 structure lacks functional moieties that could be exploited for derivatization, in this work we explored a synthetic pathway for the synthesis of a PBR28 derivative carrying an alkyne group (PBR-alkyne), enabling the fast conjugation of the ligand through azide-alkyne cycloaddition, also known as click-chemistry. As a proof of concept, we demonstrated in silico that the derivatized PBR28 ligand maintains the capability to fit into the TSPO binding pocked, and we successfully exploited PBR-alkyne to decorate zwitterionic biodegradable polymer nanoparticles (NPs) resulting in efficient internalization in cultured microglia-like cell lines. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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11 pages, 3559 KiB

Open AccessFeature PaperArticle

Isolation and Quantification of miRNA from the Biomolecular Corona on Mesoporous Silica Nanoparticles

by Carla Vidaurre-Agut, Eva María Rivero-Buceta, Christopher C. Landry and Pablo Botella

Nanomaterials 2021, 11(5), 1196; https://doi.org/10.3390/nano11051196 - 1 May 2021

Cited by 4 | Viewed by 2132

Abstract

To understand the factors that control the formation of the biomolecular corona, a systematic study of the adsorption of several miRNAs shown to be important in prostate cancer on amine-functionalized mesoporous silica nanoparticles (MSN-NH₂) has been performed. Process parameters including miRNA type, nanoparticle concentration, incubation temperature and incubation time were investigated, as well as the potential competition for adsorption between different miRNA molecules. The influence of proteins and particle PEGylation on miRNA adsorption were also explored. We found that low particle concentrations and physiological temperature both led to increased miRNA adsorption. Adsorption of miRNA was also higher when proteins were present in the same solution; reducing or preventing protein adsorption by PEGylating the MSNs hindered adsorption. Finally, the amount of miRNA adsorbed from human serum by MSN-NH₂ was compared to a commercial miRNA purification kit (TaqMan^®, Life Technologies, Carlsbad, CA, USA). MSN-NH₂ adsorbed six times as much miRNA as the commercial kit, demonstrating higher sensitivity to subtle up- and downregulation of circulating miRNA in the blood of patients. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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17 pages, 4645 KiB

Open AccessArticle

Internal Structure of Thermoresponsive Physically Crosslinked Nanogel of Poly[N-(2-hydroxypropyl)methacrylamide]-Block-Poly[N-(2,2-difluoroethyl)acrylamide], Prominent ¹⁹F MRI Tracer

by David Babuka, Kristyna Kolouchova, Ondrej Groborz, Zdenek Tosner, Alexander Zhigunov, Petr Stepanek and Martin Hruby

Nanomaterials 2020, 10(11), 2231; https://doi.org/10.3390/nano10112231 - 10 Nov 2020

Cited by 14 | Viewed by 2688

Abstract

Fluorine-19 MRI is a promising noninvasive diagnostic method. However, the absence of a nontoxic fluorine-19 MRI tracer that does not suffer from poor biodistribution as a result of its strong fluorophilicity is a constant hurdle in the widespread applicability of this otherwise versatile diagnostic technique. The poly[N-(2-hydroxypropyl)methacrylamide]-block-poly[N-(2,2-difluoroethyl)acrylamide] thermoresponsive copolymer was proposed as an alternative fluorine-19 MRI tracer capable of overcoming such shortcomings. In this paper, the internal structure of self-assembled particles of this copolymer was investigated by various methods including 1D and 2D NMR, dynamic light scattering (DLS), small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS). The elucidated structure appears to be that of a nanogel with greatly swollen hydrophilic chains and tightly packed thermoresponsive chains forming a network within the nanogel particles, which become more hydrophobic with increasing temperature. Its capacity to provide a measurable fluorine-19 NMR signal in its aggregated state at human body temperature was also investigated and confirmed. This capacity stems from the different fluorine-19 nuclei relaxation properties compared to those of hydrogen-1 nuclei. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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14 pages, 1717 KiB

Open AccessArticle

Ultrabright Fluorescent Silica Nanoparticles for Multiplexed Detection

by Saquib Ahmed M. A. Peerzade, Nadezda Makarova and Igor Sokolov

Nanomaterials 2020, 10(5), 905; https://doi.org/10.3390/nano10050905 - 8 May 2020

Cited by 6 | Viewed by 2900

Abstract

Fluorescent tagging is a popular method in biomedical research. Using multiple taggants of different but resolvable fluorescent spectra simultaneously (multiplexing), it is possible to obtain more comprehensive and faster information about various biochemical reactions and diseases, for example, in the method of flow cytometry. Here we report on a first demonstration of the synthesis of ultrabright fluorescent silica nanoporous nanoparticles (Star-dots), which have a large number of complex fluorescence spectra suitable for multiplexed applications. The spectra are obtained via simple physical mixing of different commercially available fluorescent dyes in a synthesizing bath. The resulting particles contain dye molecules encapsulated inside of cylindrical nanochannels of the silica matrix. The distance between the dye molecules is sufficiently small to attain Forster resonance energy transfer (FRET) coupling within a portion of the encapsulated dye molecules. As a result, one can have particles of multiple spectra that can be excited with just one wavelength. We show this for the mixing of five, three, and two dyes. Furthermore, the dyes can be mixed inside of particles in different proportions. This brings another dimension in the complexity of the obtained spectra and makes the number of different resolvable spectra practically unlimited. We demonstrate that the spectra obtained by different mixing of just two dyes inside of each particle can be easily distinguished by using a linear decomposition method. As a practical example, the errors of demultiplexing are measured when sets of a hundred particles are used for tagging. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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16 pages, 3205 KiB

Open AccessArticle

Internalized FGF-2-Loaded Nanoparticles Increase Nuclear ERK1/2 Content and Result in Lung Cancer Cell Death

by Tianxin Miao, Andrew C. Little, Alexander Aronshtam, Taylor Marquis, Spencer L. Fenn, Milena Hristova, Dimitry N. Krementsov, Albert van der Vliet, Jeffrey L. Spees and Rachael A. Oldinski

Nanomaterials 2020, 10(4), 612; https://doi.org/10.3390/nano10040612 - 27 Mar 2020

Cited by 10 | Viewed by 3239

Abstract

Innovative cancer treatments, which improve adjuvant therapy and reduce adverse events, are desperately needed. Nanoparticles provide controlled intracellular biomolecule delivery in the absence of activating external cell surface receptors. Prior reports suggest that intracrine signaling, following overexpression of basic fibroblast growth factor (FGF-2) after viral transduction, has a toxic effect on diseased cells. Herein, the research goals were to (1) encapsulate recombinant FGF-2 within stable, alginate-based nanoparticles (ABNs) for non-specific cellular uptake, and (2) determine the effects of ABN-mediated intracellular delivery of FGF-2 on cancer cell proliferation/survival. In culture, human alveolar adenocarcinoma basal epithelial cell line (A549s) and immortalized human bronchial epithelial cell line (HBE1s) internalized ABNs through non-selective endocytosis. Compared to A549s exposed to empty (i.e., blank) ABNs, the intracellular delivery of FGF-2 via ABNs significantly increased the levels of lactate dehydrogenase, indicating that FGF-2-ABN treatment decreased the transformed cell integrity. Noticeably, the nontransformed cells were not significantly affected by FGF-2-loaded ABN treatment. Furthermore, FGF-2-loaded ABNs significantly increased nuclear levels of activated-extracellular signal-regulated kinase ½ (ERK1/2) in A549s but had no significant effect on HBE1 nuclear ERK1/2 expression. Our novel intracellular delivery method of FGF-2 via nanoparticles resulted in increased cancer cell death via increased nuclear ERK1/2 activation. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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14 pages, 3971 KiB

Open AccessArticle

Evaluation of the Cytotoxicity and Oxidative Stress Response of CeO₂-RGO Nanocomposites in Human Lung Epithelial A549 Cells

by Maqusood Ahamed, Mohd Javed Akhtar, M. A. Majeed Khan, ZabnAllah M. Alaizeri and Hisham A. Alhadlaq

Nanomaterials 2019, 9(12), 1709; https://doi.org/10.3390/nano9121709 - 29 Nov 2019

Cited by 31 | Viewed by 3636

Abstract

Graphene-based nanocomposites have attracted enormous interest in nanomedicine and environmental remediation, owing to their unique characteristics. The increased production and widespread application of these nanocomposites might raise concern about their adverse health effects. In this study, for the first time, we examine the cytotoxicity and oxidative stress response of a relatively new nanocomposite of cerium oxide-reduced graphene oxide (CeO₂-RGO) in human lung epithelial (A549) cells. CeO₂-RGO nanocomposites and RGO were prepared by a simple hydrothermal method and characterized by relevant analytical techniques. Cytotoxicity data have shown that RGO significantly induces toxicity in A549 cells, evident by cell viability reduction, membrane damage, cell cycle arrest, and mitochondrial membrane potential loss. However, CeO₂-RGO nanocomposites did not cause statistically significant toxicity as compared to a control. We further observed that RGO significantly induces reactive oxygen species generation and reduces glutathione levels. However, CeO₂-RGO nanocomposites did not induce oxidative stress in A549 cells. Interestingly, we observed that CeO₂ nanoparticles (NPs) alone significantly increase glutathione (GSH) levels in A549 cells as compared to a control. The GSH replenishing potential of CeO₂ nanoparticles could be one of the possible reasons for the biocompatible nature of CeO₂-RGO nanocomposites. Our data warrant further and more advanced research to explore the biocompatibility/safety mechanisms of CeO₂-RGO nanocomposites in different cell lines and animal models. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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20 pages, 2963 KiB

Open AccessArticle

Development of Superparamagnetic Nanoparticles Coated with Polyacrylic Acid and Aluminum Hydroxide as an Efficient Contrast Agent for Multimodal Imaging

by Manuel Antonio González-Gómez, Sarah Belderbos, Susana Yañez-Vilar, Yolanda Piñeiro, Frederik Cleeren, Guy Bormans, Christophe M. Deroose, Willy Gsell, Uwe Himmelreich and José Rivas

Nanomaterials 2019, 9(11), 1626; https://doi.org/10.3390/nano9111626 - 15 Nov 2019

Cited by 60 | Viewed by 4917

Abstract

Early diagnosis of disease and follow-up of therapy is of vital importance for appropriate patient management since it allows rapid treatment, thereby reducing mortality and improving health and quality of life with lower expenditure for health care systems. New approaches include nanomedicine-based diagnosis combined with therapy. Nanoparticles (NPs), as contrast agents for in vivo diagnosis, have the advantage of combining several imaging agents that are visible using different modalities, thereby achieving high spatial resolution, high sensitivity, high specificity, morphological, and functional information. In this work, we present the development of aluminum hydroxide nanostructures embedded with polyacrylic acid (PAA) coated iron oxide superparamagnetic nanoparticles, Fe₃O₄@Al(OH)₃, synthesized by a two-step co-precipitation and forced hydrolysis method, their physicochemical characterization and first biomedical studies as dual magnetic resonance imaging (MRI)/positron emission tomography (PET) contrast agents for cell imaging. The so-prepared NPs are size-controlled, with diameters below 250 nm, completely and homogeneously coated with an Al(OH)₃ phase over the magnetite cores, superparamagnetic with high saturation magnetization value (Ms = 63 emu/g-Fe₃O₄), and porous at the surface with a chemical affinity for fluoride ion adsorption. The suitability as MRI and PET contrast agents was tested showing high transversal relaxivity (r₂) (83.6 mM⁻¹ s⁻¹) and rapid uptake of ¹⁸F-labeled fluoride ions as a PET tracer. The loading stability with ¹⁸F-fluoride was tested in longitudinal experiments using water, buffer, and cell culture media. Even though the stability of the ¹⁸F-label varied, it remained stable under all conditions. A first in vivo experiment indicates the suitability of Fe₃O₄@Al(OH)₃ nanoparticles as a dual contrast agent for sensitive short-term (PET) and high-resolution long-term imaging (MRI). Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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11 pages, 6039 KiB

Open AccessArticle

Interaction of Immune Cells and Tumor Cells in Gold Nanorod–Gelatin Composite Porous Scaffolds

by Xiuhui Wang, Naoki Kawazoe and Guoping Chen

Nanomaterials 2019, 9(10), 1367; https://doi.org/10.3390/nano9101367 - 24 Sep 2019

Cited by 4 | Viewed by 2715

Abstract

Composite porous scaffolds prepared by immobilization of photothermal nano-agents into porous scaffold have been used for both cancer therapy and tissue regeneration. However, it is not clear how the host immune cells and ablated tumor cells interact and stimulate each other in the composite scaffolds. In this research, a gold nanorod-incorporated gelatin composite scaffold with controlled spherical large pores and well interconnected small pores was fabricated by using ice particulates as a porogen. The composite porous scaffold was used for investigating the interaction between dendritic cells and photothermally ablated breast tumor cells. The composite scaffold demonstrated excellent photothermal property and the temperature change value could be adjusted by irradiation time and laser power density. The composite scaffold showed excellent photothermal ablation ability towards breast tumor cells. The photothermally ablated tumor cells induced activation of dendritic cells when immature dendritic cells were co-cultured in the composite scaffold. Consequently, the gold nanorod–incorporated gelatin composite porous scaffold should provide a useful platform for simultaneous photothermal-immune ablation of breast tumor. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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Review

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41 pages, 39907 KiB

Open AccessReview

The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors

by Kyle M. Pierce, William R. Miklavcic, Kyle P. Cook, Mikayla Sweitzer Hennen, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks, Jessica E. Pullan and Kaitlin M. Dailey

Nanomaterials 2021, 11(11), 3018; https://doi.org/10.3390/nano11113018 - 10 Nov 2021

Cited by 12 | Viewed by 3918

Abstract

While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap is substantial enough that breakthroughs in one therapeutic could have considerable implications on the progression of the other two. Each oncotherapeutic modality has accomplished clinical translation, successfully overcoming the potential pitfalls promising therapeutics face. However, once studies enter clinical trials, the data all but disappears, leaving pre-clinical researchers largely in the dark. Overall, the creativity, flexibility, and innovation of these modalities for solid tumor treatments are greatly encouraging, and usher in a new age of pharmaceutical development. Full article

(This article belongs to the Special Issue Frontiers in Nanomaterials for Clinical Imaging and Selective Therapy)

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