Application of molecularly imprinted polymers as artificial receptors for imaging.

Medical diagnostics aims at specific localization of molecular targets as well as detection of abnormalities associated with numerous diseases. Molecularly imprinted polymers (MIPs) represent an approach of creating a synthetic material exhibiting selective recognition properties toward the desired template. The fabricated target-specific MIPs are usually well reproducible, economically efficient, and stable under critical conditions as compared to routinely used biorecognition elements such as fluorescent proteins, antibodies, enzymes, or aptamers and can even be created to those targets for which no antibodies are available. In this review, we summarize the methods of polymer fabrication. Further, we provide key for selection of the core material with imaging function depending on the imaging modality used. Finally, MIP-based imaging applications are highlighted and presented in a comprehensive form from different aspects. STATEMENT OF SIGNIFICANCE: In this review, we summarize the methods of polymer fabrication. Key applications of Molecularly imprinted polymers (MIPs) in imaging are highlighted and discussed with regard to the selection of the core material for imaging as well as commonly used imaging targets. MIPs represent an approach of creating a synthetic material exhibiting selective recognition properties toward the desired template. The fabricated target-specific MIPs are usually well reproducible, economically efficient, and stable under critical conditions as compared to routinely used biorecognition elements, e.g., antibodies, fluorescent proteins, enzymes, or aptamers, and can even be created to those targets for which no antibodies are available.

CdS quantum dots-based immunoassay combined with particle imprinted polymer technology and laser ablation ICP-MS as a versatile tool for protein detection.

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.

Molecularly imprinted polymers coupled to mass spectrometric detection for metallothionein sensing.

We report a facile method for detection of metallothionein (MT), a promising clinically relevant biomarker, in spiked plasma samples. This method, for the first time, integrates molecularly imprinted polymers as purification/pretreatment step with matrix assisted laser desorption/ionization time-of-flight mass spectrometric detection and with laser ablation inductively coupled plasma mass spectrometry for analysis of MTs. The prepared MT-imprinted polydopamine layer showed high binding capacity and specific recognition properties toward the template. Optimal monomer (dopamine) concentration was found to be 16 mM of dopamine. This experimental setup allows to measure µM concentrations of MT that are present in blood as this can be used for clinical studies recognizing MT as marker of various diseases including tumour one. Presented approach not only provides fast sample throughput but also avoids the limitations of methods based on use of antibodies (e.g. high price, cross-reactivity, limited availability in some cases, etc.).

Designing next generation of photon upconversion: Recent advances in organic triplet-triplet annihilation upconversion nanoparticles.

Organic triplet-triplet annihilation upconversion (TTA-UC) nanoparticles have emerged as exciting therapeutic agents and imaging probes in recent years due to their unique chemical and optical properties such as outstanding biocompatibility and low power excitation density. In this review, we focus on the latest breakthroughs in such new version of upconversion nanoparticle, including their design, preparation, and applications. First, we will discuss the key principles and design concept of these organic-based photon upconversion in regard to the methods of selection of the related triplet TTA dye pairs (photosensitizer and emitter). Then, we will discuss the recent approaches s to construct TTA-UCNPs including silica TTA-UCNPs, lipid-coated TTA-UCNPs, polymer encapsulated TTA-UCNPs, nano-droplet TTA-UCNPs and metal-organic frameworks (MOFs) constructed TTA-UCNPs. In addition, the applications of TTA-UCNPs will be discussed. Finally, we will discuss the challenges posed by current TTA-UCNP development.

Upconversion nanoparticle bioconjugates characterized by capillary electrophoresis.

Upconversion nanoparticles (UCNPs) are an emerging class of optical materials with high potential in bioimaging due to practically no background signal and high penetration depth. Their excellent optical properties and easy surface functionalization make them perfect for conjugation with targeting ligands. In this work, capillary electrophoretic (CE) method with laser-induced fluorescence detection was used to investigate the behavior of carboxyl-silica-coated UCNPs. Folic acid, targeting folate receptor overexpressed by wide variety of cancer cells, was used for illustrative purposes and assessed by CE under optimized conditions. Peptide-mediated bioconjugation of antibodies to UCNPs was also investigated. Despite the numerous advantages of CE, this is the first time that CE was employed for characterization of UCNPs and their bioconjugates. The separation conditions were optimized including the background electrolyte concentration and pH. The optimized electrolyte was 20 mM borate buffer with pH 8.