Bioimaging of hyaluronic acid derivatives using nanosized carbon dots.

Fluorescent nanosized carbon dots (Cdots) are an emerging bioimaging agent with excellent chemical inertness and marginal cytotoxicity in comparison to widely used semiconductor quantum dots. In this work, we report the application of Cdots for real time bioimaging of target specific delivery of hyaluronic acid (HA) derivatives. Polyethylene glycol (PEG) diamine-capped Cdots were synthesized by the pyrolysis of citric acid in a hot solvent. The synthesized Cdots showed strong fluorescence under UV excitation with emission properties dependending on the excitation wavelength. HA-Cdot conjugates were synthesized by amide bond formation between amine groups of Cdot and carboxylic groups of HA. After confirmation of the negligible cytotoxicity of Cdots and HA-Cdot conjugates, in vitro bioimaging was carried out for target specific intracellular delivery of the HA-Cdot conjugates by HA receptor-mediated endocytosis. Furthermore, in vivo real-time bioimaging of Cdots and HA-Cdot conjugates exhibited the target specific delivery of HA-Cdot conjugates to the liver with abundant HA receptors. Taken together, we could confirm the feasibility of HA derivatives as a target-specific drug delivery carrier for the treatment of liver diseases and Cdots as a promising bioimaging agent.

Development of a DNA isolation device using poly(3,4-dihydroxy-L-phenylalanine)-coated swab for on-site molecular diagnostics.

For on-site molecular diagnostics, a pre-treatment step for isolation of nucleic acid from clinical samples on site is desired. However, conventional commercialized silica-based nucleic acid isolation kits require repetitive pipetting and a centrifugation or permanent magnet for buffer exchange. In this study, we developed a poly(3,4-dihydroxy-L-phenylalanine) (L-DOPA)-coated swab that can absorb and desorb DNA depending on pH of buffers and a portable integrated DNA isolation device that comprises integrated chambers containing DNA isolation buffers. The poly(L-DOPA)-coated swab interacts with each buffer by passing through the membrane between the integrated chambers. Our device involves a simple operation and does not require any large equipment or skilled experts. By connecting the device with an automated polymerase chain reaction system, an isothermal amplification system, or a non-amplified DNA detection method, on-site molecular diagnosis of various diseases can be quickly realized.

Biodegradable Photonic Melanoidin for Theranostic Applications.

Light-absorbing nanoparticles for localized heat generation in tissues have various biomedical applications in diagnostic imaging, surgery, and therapies. Although numerous plasmonic and carbon-based nanoparticles with strong optical absorption have been developed, their clearance, potential cytotoxicity, and long-term safety issues remain unresolved. Here, we show that "generally regarded as safe (GRAS)" melanoidins prepared from glucose and amino acid offer a high light-to-heat conversion efficiency, biocompatibility, biodegradability, nonmutagenicity, and efficient renal clearance, as well as a low cost for synthesis. We exhibit a wide range of biomedical photonic applications of melanoidins, including in vivo photoacoustic mapping of sentinel lymph nodes, photoacoustic tracking of gastrointestinal tracts, photothermal cancer therapy, and photothermal lipolysis. The biodegradation rate and renal clearance of melanoidins are controllable by design. Our results confirm the feasibility of biodegradable melanoidins for various photonic applications to theranostic nanomedicines.

Surface modification of multipass caliber-rolled Ti alloy with dexamethasone-loaded graphene for dental applications.

Titanium (Ti) and its alloys with a high mechanical strength and a small diameter can be effectively exploited for minimally invasive dental implantation. Here, we report a multipass caliber-rolled Ti alloy of Ti13Nb13Zr (MPCR-TNZ) with a high mechanical strength and strong fatigue characteristics. For further dental applications, MPCR-TNZ was surface-modified with reduced graphene oxide (RGO) and loaded with osteogenic dexamethasone (Dex) via π-π stacking on the graphitic domain of RGO. The Dex-loaded RGO-MPCR-TNZ (Dex/RGO-MPCR-TNZ) resulted in significantly enhanced growth and differentiation of MC3T3-E1 cells into osteoblasts, which was confirmed by Alizarin red staining, alkaline phosphatase activity test, immunocytochemistry, and real-time PCR. Moreover, we could confirm the feasibility of Dex/RGO-MPCR-TNZ from the implantation test of a prototype of a dental implant to an artificial bone block for clinical dental applications.

Self-assembled complex of probe peptide--E. Coli RNA I conjugate and nano graphene oxide for apoptosis diagnosis.

Caspase-3 plays an important role in the initiation and propagation of apoptosis which is involved in various kinds of diseases including neurodegenerative diseases and inflammatory diseases. The capase-3 cleavable site of Asp-Glu-Val-Asp (DEVD) connected to a partial sequence of Escherichia coli RNAI was labeled with tetramethyl-6-carboxyrhodamine (TAMRA) as an optical probe. Graphene oxide (GO) was synthesized by a modified Hummer's method and exploited for the preparation of nano-sized GO (NGO) conjugated with polyethylene glycol (PEG). After binding the NGO-PEG by π-π stacking, the quenched fluorescence of TAMRA-DEVD-single stranded DNA (ssDNA) conjugate was recovered via the enzymatic cleavage by caspase-3 in live A549 cells. The comparative study with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay clearly confirmed the specific detection of apoptosis by the non-covalent TAMRA-DEVD-ssDNA/NGO-PEG complex. Furthermore, the self-assembled NGO complex was successfully exploited for in vivo diagnosis of apoptosis-related diseases like hypoxic-ischemic encephalopathy (HIE) and liver cirrhosis.