Highly fluorescent oligodopamine (F-ODA) for accurate and sensitive detection of the neurotransmitter dopamine.

Dopamine (DA) is an important neurotransmitter for regulating the central nervous system, hormones, and cardiovascular system. Fluorescence technique is usually applied for the rapid detection of DA neurotransmitter because DA is easily converted to fluorescent products under alkaline condition. However, it is difficult to accurately quantify low levels of DA (<10 nM) because the final product of DA conversion, so-called polydopamine (PDA), usually have low fluorescence efficiency. In this study, DA dissolved in Tris-EDTA buffer (pH 8.5) was oxidized and polymerized by adding NaOH as an oxidizing agent. After obtaining products with various degrees of polymerization, the fluorescent oligodopamine (F-ODA) (i.e., indole-5,6-quinone-rich compounds) was separated from non-fluorescent polydopamine (PDA) products. After removing non-fluorescent PDA by centrifugation, the F-ODA in the supernatant exhibited high FL intensity at 470 nm under excitation at 360 nm. At the optimal reaction conditions, the standard curve of the F-ODA exhibited a good linearity over wide range of DA concentration from 1 µM to 1 nM (limit of detection = ~0.1 nM), suggesting a very useful analytical tool for the accurate and sensitive detection of the neurotransmitter DA in bio-fluid.

Hierarchical Au nanoclusters electrodeposited on amine-terminated ITO glass as a SERS-active substrate for the reliable and sensitive detection of serotonin in a Tris-HCl buffer solution.

Although serotonin (5-HT) is one of the most important neurotransmitters that are responsible for critical roles in the central nervous system, only few studies have been reported on the reliable and sensitive detection of 5-HT by the SERS technique owing to the lower Raman cross-section and lack of a common extraction method of 5-HT. In this study, a SERS-active substrate was fabricated by electrodepositing hierarchical Au nanostructures on amine-terminated ITO (indium tin oxide) glass to achieve an enhanced Raman signal of 5-HT. The electrodeposition process was performed by applying the nucleation potential E1 = 0.7 V for 2 s and the growth potential E2 = -0.2 V for 1000 s for repeated cycles. As a testing analyte, 5-HT was dissolved in four different solvents i.e. PBS buffer, Tris-HCl buffer, distilled water, and ethanol solution (20%). Among them, Tris-HCl buffer produced the most sensitive and reproducible Raman signals for 5-HT along with the lowest detection limit of ∼10-9 M due to the strong adsorption interactions between the Au surface and the indole amine groups of 5-HT under alkaline conditions. Surprisingly, the standard curve between the Raman intensity at 751 cm-1 and the log-scale concentration of 5-HT showed a linear dynamic range of over five orders of magnitude in the Tris-HCl buffer solution, suggesting a possible quantification of the 5-HT level in a biological fluid with 5-HT dysfunction or deficiency.

Facile synthesis of boronic acid-functionalized magnetic nanoparticles for efficient dopamine extraction.

Because dopamine (DA) is one of the most critical neurotransmitters that influence a wide variety of motivated human behaviors, it is necessary to develop a facile diagnostic tool that can quantify the physiological level. In this study, core-shell magnetic silica nanoparticles (Fe3O4@SiO2) were prepared using a modified sol-gel reaction. The Fe3O4@SiO2 were functionalized using 3-aminophenylboronic acid (APBA) via a facile and rapid synthetic route, hereafter referred to as Fe3O4@SiO2@APBA The resultant Fe3O4@SiO2@APBA not only adsorbed DA molecules, but also were easily separated from solution using a simple magnetic manipulation. The adsorbed amounts of DA by the Fe3O4@SiO2@APBA were quantified by measuring the changes in fluorescence intensity of polydopamine (at 463 nm) originated from the self-polymerized DA remained in the supernatant before and after the adsorption process. The Fe3O4@SiO2@APBA exhibited two-stage adsorption behavior for DA, and the maximal adsorption capacity was 108.46 µg/g at pH 8.5. Our particle system demonstrated the potential application for extracting compounds with cis-diols (including catechol amines) from the biological fluid.

Targeted and controlled drug delivery by multifunctional mesoporous silica nanoparticles with internal fluorescent conjugates and external polydopamine and graphene oxide layers.

This study demonstrated the targeted delivery and controlled release of cisplatin drug molecules from doubly decorated mesoporous silica nanoparticles (MSNs), which were internally grafted with fluorescent conjugates and externally coated with polydopamine (PDA) and graphene oxide (GO) layers. The brush-like internal conjugates conferred fluorescent functionality and high capacity of cisplatin loading into MSNs, as well as contributing to a sustained release of the cisplatin through a porous channel with the assistance of external PDA layer. A consolidated double-layer formed by electrostatic interactions between the GO nanosheet and the PDA layer induced more controlled release kinetics which was well predicted by Higuchi model. In addition, Our MSNs exhibited stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent against cancer cells. In a cell test, multifunctional MSNs showed a low toxicity itself, but gave a high cytotoxicity against human epithelial neuroblastoma cells (SH-SY5Y) after loading cisplatin. Notably, GO-wrapped MSNs exhibited very effective drug delivery because GO wrapping enhanced their dispensability in aqueous solution, photothermal heating effect, and efficient endocytosis into cells. Furthermore, monoclonal antibody (anti-human epidermal growth factor receptor)-conjugated MSNs showed a higher specificity, which resulted in more enhanced anticancer effects in vitro. The current study demonstrated a reliable synthesis of multifunctional MSNs, endowed with fluorescent imaging, stimuli-responsive controlled release, higher specificity, and efficient cytotoxicity toward cancer cells. STATEMENT OF SIGNIFICANCE: The current study demonstrated the reliable synthesis of multifunctional mesoporous silica nanoparticles (MSNs) with internal fluorescent conjugates and external polydopamine and graphene oxide (GO) layers. The combination of internal conjugates and external coating layers produced an effective pore closure effect, leading to controlled and sustained release of small drug molecules. Notably, GO wrapping improved the dispensability and cellular uptake of the MSNs, as well as enhanced drug-controlled release. Our multifunctional MSNs revealed very efficient drug delivery effects against human epithelial neuroblastoma cells by demonstrating several strengths: i) fluorescent imaging, ii) sustained and controlled release of small drug molecules, iii) efficient cellular uptake, cytotoxicity and specificity, and v) stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent.