19F magnetic resonance imaging (MRI) using fluoropolymer tracers has recently emerged as a promising, non-invasive diagnostic tool in modern medicine. However, despite its potential, 19F MRI remains overlooked and underused due to the limited availability or unfavorable properties of fluorinated tracers. Herein, we report a straightforward synthetic route to highly fluorinated 19F MRI nanotracers via aqueous dispersion polymerization-induced self-assembly of a water-soluble fluorinated monomer. A polyethylene glycol-based macromolecular chain-transfer agent was extended by RAFT-mediated N-(2,2,2-trifluoroethyl)acrylamide (TFEAM) polymerization in water, providing fluorine-rich self-assembled nanoparticles in a single step. The resulting nanoparticles had different morphologies and sizes ranging from 60 to 220 nm. After optimizing their structure to maximize the magnetic relaxation of the fluorinated core, we obtained a strong 19F NMR/MRI signal in an aqueous environment. Their non-toxicity was confirmed on primary human dermal fibroblasts. Moreover, we visualized the nanoparticles by 19F MRI, both in vitro (in aqueous phantoms) and in vivo (after subcutaneous injection in mice), thus confirming their biomedical potential.
- MeSH
- Acrylamide MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Mice MeSH
- Nanoparticles * chemistry MeSH
- Polymerization MeSH
- Water * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Theranostics is a novel paradigm integrating therapy and diagnostics, thereby providing new prospects for overcoming the limitations of traditional treatments. In this context, perfluorocarbons (PFCs) are the most widely used tracers in preclinical fluorine-19 magnetic resonance (19F MR), primarily for their high fluorine content. However, PFCs are extremely hydrophobic, and their solutions often display reduced biocompatibility, relative instability, and subpar 19F MR relaxation times. This study aims to explore the potential of micellar 19F MR imaging (MRI) tracers, synthesized by polymerization-induced self-assembly (PISA), as alternative theranostic agents for simultaneous imaging and release of the non-steroidal antileprotic drug clofazimine. In vitro, under physiological conditions, these micelles demonstrate sustained drug release. In vivo, throughout the drug release process, they provide a highly specific and sensitive 19F MRI signal. Even after extended exposure, these fluoropolymer tracers show biocompatibility, as confirmed by the histological analysis. Moreover, the characteristics of these polymers can be broadly adjusted by design to meet the wide range of criteria for preclinical and clinical settings. Therefore, micellar 19F MRI tracers display physicochemical properties suitable for in vivo imaging, such as relaxation times and non-toxicity, and high performance as drug carriers, highlighting their potential as both diagnostic and therapeutic tools.
- MeSH
- Biocompatible Materials chemistry MeSH
- Fluorine chemistry MeSH
- Fluorocarbons chemistry MeSH
- Halogenation MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Micelles MeSH
- Mice MeSH
- Nanoparticles * chemistry therapeutic use MeSH
- Theranostic Nanomedicine * MeSH
- Fluorine-19 Magnetic Resonance Imaging * methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Stimuli-responsive copolymers are of great interest for targeted drug delivery. This study reports on a controllable post-polymerization quaternization with 2-bromomethyl-4-fluorophenylboronic acid of the poly(4-vinyl pyridine) (P4VP) block of a common poly(styrene)-b-poly(4-vinyl pyridine)-b-poly(ethylene oxide) (SVE) triblock terpolymer in order to achieve a selective responsivity to various diols. For this purpose, a reproducible method was established for P4VP block quaternization at a defined ratio, confirming the reaction yield by 11B, 1H NMR. Then, a reproducible self-assembly protocol is designed for preparing stable micelles from functionalized stimuli-responsive triblock terpolymers, which are characterized by light scattering and by cryogenic transmission electron microscopy. In addition, UV-Vis spectroscopy is used to monitor the boron-ester bonding and hydrolysis with alizarin as a model drug and to study encapsulation and release of this drug, induced by sensing with three geminal diols: fructose, galactose and ascorbic acid. The obtained results show that only the latter, with the vicinal diol group on sp2-hybridized carbons, was efficient for alizarin release. Therefore, the post-polymerization method for triblock terpolymer functionalization presented in this study allows for preparation of specific stimuli-responsive systems with a high potential for targeted drug delivery, especially for cancer treatment.
- Publication type
- Journal Article MeSH
For the first time, the combination of molecularly imprinted polymer (MIP) technology with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is presented with focus on an optimization of the LA-ICP-MS parameters such as laser beam diameter, laser beam fluence, and scan speed using CdS quantum dots (QDs) as a template and dopamine as a functional monomer. A non-covalent imprinting approach was employed in this study due to the simplicity of preparation. Simple oxidative polymerization of the dopamine that creates the self-assembly monolayer seems to be an ideal choice. The QDs prepared by UV light irradiation synthesis were stabilized by using mercaptosuccinic acid. Formation of a complex of QD-antibody and QD-antibody-antigen was verified by using capillary electrophoresis with laser-induced fluorescence detection. QDs and antibody were connected together via an affinity peptide linker. LA-ICP-MS was employed as a proof-of-concept for detection method of two types of immunoassay: 1) antigen extracted from the sample by MIP and subsequently overlaid/immunoreacted by QD-labelled antibodies, 2) complex of antigen, antibody, and QD formed in the sample and subsequently extracted by MIP. The first approach provided higher sensitivity (MIP/NIP), however, the second demonstrated higher selectivity. A mixture of proteins with size in range 10-250 kDa was used as a model sample to demonstrate the capability of both approaches for detection of IgG in a complex sample.
- MeSH
- Electrophoresis, Capillary MeSH
- Fluorescence MeSH
- Mass Spectrometry * MeSH
- Immunoassay methods MeSH
- Immunoglobulin G analysis MeSH
- Quantum Dots chemistry MeSH
- Laser Therapy * MeSH
- Molecular Imprinting * MeSH
- Mice MeSH
- Signal Processing, Computer-Assisted MeSH
- Polymers chemistry MeSH
- Proteins analysis MeSH
- Cadmium Compounds chemistry MeSH
- Sulfides chemistry MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
... of Tertiary Structure 70 -- Proteins Associate into Multimeric Structures and -- Macromolecular Assemblies ... ... 722 -- Capping Proteins Block Assembly and Disassembly at Actin Filament Ends 722 -- I Mechanisms of ... ... Actin Filament Assembly 723 -- Formins Assemble Unbranched Filaments 723 -- The Arp2/3 Complex Nucleates ... ... Branched Filament -- Assembly 724 -- Intracellular Movements Can Be Powered by Actin -- Polymerization ... ... and \"Search-and-Capture\" -- Help Organize Microtubules 766 -- Drugs Affecting Tubulin Polymerization ...
6th ed. xxxvii, 1150 s. : il., tab. ; 29 cm
- MeSH
- Cell Biology MeSH
- Molecular Biology MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- NML Fields
- biologie
- cytologie, klinická cytologie
... -- Nerve Cells Allow a Rapid Adaptation to a Changing -- World 35 -- Developing Nerve Cells Must Assemble ... ... Proteins Often Evolve Through the Combination 82 of Different Polypeptide Domains -- Protein Subunits Can Self-assemble ... ... Single Type of Protein Subunit Can Interact with 84 Itself to Form Geometrically Regular Aggregates Self-assembling ... ... - 115 -- 118 -- 118 -- 118 -- 120 -- 121 -- 121 -- 124 -- List of Topics xi -- There Are Limits to Self-assembly ... ... Composition 696 -- During Secretion, Procollagen Molecules Are Cleaved to Form Collagen Molecules, Which Self-assemble ...
xxxix, 1146 s. : il., tab. ; 28 cm
- MeSH
- Cell Biology MeSH
- Molecular Biology MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- NML Fields
- biologie
- cytologie, klinická cytologie
... That Act Through Cytokine Receptors and the JAK-STAT Signaling -- Pathway 864 -- PANEL 16-2 The Polymerization ... ... of Large Structures 127 -- Many Structures in Cells Are Capable of Self-Assembly 128 -- Assembly Factors ... ... 384 -- Eukaryotic Transcription Regulators Work in Groups 385 -- Activator Proteins Promote the Assembly ... ... Negative Feedback Is a Powerful Strategy in Cell Regulation 515 -- Delayed Negative Feedback Can Induce ... ... -Cdk Initiates Spindle Assembly in Prophase The Completion of Spindle Assembly in Animal Cells Requires ...
Sixth edition xxxiv, 1430 stran v různém stránkování : ilustrace (převážně barevné) ; 29 cm
- MeSH
- Cells * MeSH
- Molecular Biology MeSH
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- NML Fields
- molekulární biologie, molekulární medicína
- NML Publication type
- učebnice vysokých škol
... Contents -- Introduction: Cells as macromolecular assemblies -- 1: Proteins -- Macromolecules are assembled ... ... by polymerizing small molecules -- Proteins consist of chains of amino acids -- Protein conformation ... ... Structural gene clusters are coordinately controlled Repressor is controlled by a small molecule inducer ... ... -- 338 -- 340 -- 343 xii I Contents -- Repressor protein binds to the operator and is released by inducer ... ... membrane 1056 -- G proteins may activate or inhibit target proteins 1061 -- Protein tyrosine kinases induce ...
xviii, 1260 stran : ilustrace ; 28 cm
... barriers are the first defense against pathogens. 1 -3 The immune system is activated by inflammatory inducers ... ... Sensor cells express pattern recognition receptors that provide an initial discrimination between self ... ... and nonself. 1 -6 Sensor cells induce an inflammatory response by producing mediators such as chemokines ... ... Principles of adaptive immunity. 1-8 The interaction of antigens with antigen receptors induces lymphocytes ... ... shock when released systemically. 118 -- 3-21 Cytokines made by macrophages and dendritic cells induce ...
9th edition xx, 904 stran : ilustrace, tabulky ; 28 cm
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- alergologie a imunologie
- biologie
- fyziologie
- NML Publication type
- kolektivní monografie
... Concepts in Immunology 1 -- Chapter 2 Innate Immunity: The First Lines of Defense 37 -- Chapter 3 The Induced ... ... - Principles of innate and adaptive immunity. 3 -- 1-1 The immune system recognizes infection and induces ... ... tissues throughout the body. 9 -- 1-6 Most infectious agents activate the innate immune system and induce ... ... Pattern recognition receptors of the innate immune system provide an initial discrimination between self ... ... Section references. 121 -- 122 -- 122 -- Ch apter 3 -- The Induced Responses of Innate -- Immunity 75 ...
8th ed. xix, 868 s. : il., tab.
- MeSH
- Immunity MeSH
- Immune System MeSH
- Immunotherapy MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- alergologie a imunologie
- biologie
