Biocompatible silica-overcoated magnetic nanoparticles containing an organic fluorescence dye, rhodamine B isothiocyanate (RITC), within a silica shell [50 nm size, MNP@SiO2(RITC)s] were synthesized. For future application of the MNP@SiO2(RITC)s into diverse areas of research such as drug or gene delivery, bioimaging, and biosensors, detailed information of the cellular uptake process of the nanoparticles is essential. Thus, this study was performed to elucidate the precise mechanism by which the lung cancer cells uptake the magnetic nanoparticles. Lung cells were chosen for this study because inhalation is the most likely route of exposure and lung cancer cells were also found to uptake magnetic nanoparticles rapidly in preliminary experiments. The lung cells were pretreated with different metabolic inhibitors. Our results revealed that low temperature disturbed the uptake of magnetic nanoparticles into the cells. Metabolic inhibitors also prevented the delivery of the materials into cells. Use of TEM clearly demonstrated that uptake of the nanoparticles was mediated through endosomes. Taken together, our results demonstrate that magnetic nanoparticles can be internalized into the cells through an energy-dependent endosomal-lysosomal mechanism.

Background/AimsThis study aimed to develop and validate a risk prediction model for the development of hepatocellular carcinoma (HCC) in treatment-naïve patients receiving oral antiviral treatment for chronic hepatitis B (CHB).MethodsWe investigated 2,061 Korean treatment-naïve patients with CHB treated with entecavir as an initial therapy. A risk score model for HCC development was developed based on multivariable Cox regression model in a single center (n=990) and was validated using the time-dependent area under the receiver operating characteristic curve (AUROC) in three other centers (n=1,071). The difference of HCC development among risk groups (low, intermediate, and high) categorized by risk score was also investigated.ResultsThe cumulative incidence rates of HCC at 5 years were 11.2% and 8.9% in the testing and validation cohorts, respectively. HCC-Risk Estimating Score in CHB patients Under Entecavir (HCC-RESCUE) is formulated as (age+15×gender [female=0 / male=1]+23×cirrhosis [absence=0 / presence=1]). The AUROCs at 1 year, 3 years, and 5 years were 0.82, 0.81, and 0.81, respectively, in the validation cohort. A significant difference of HCC development in each risk group was determined by the 5-year HCC risk score in the validation cohort (low risk group, 2.1%; intermediate risk group, 9.3%; high risk group, 41.2%, p<0.001).ConclusionsThe study presents a new risk score model with a good ability to predict HCC development and determine high risk patients for HCC development consisting of readily available clinical factors in treatment-naïve CHB patients receiving entecavir.

Enzyme-linked immunosorbent assays (ELISAs) have most widely been applied in immunoassays for several decades. However, several unavoidable limitations (e.g., instability caused by structural unfolding) of natural enzymes have hindered their widespread applications. Here, we describe a new nanohybrid consisting of Fe₃O₄ magnetic nanoparticles (MNPs) and platinum nanoparticles (Pt NPs), simultaneously immobilized on the surface of graphene oxide (GO). By synergistically integrating highly catalytically active Pt NPs and MNPs on GO whose frameworks possess high substrate affinity, the nanohybrid is able to achieve up to a 30-fold higher maximal reaction velocity (V(max)) compared to that of free GO for the colorimetric reaction of the peroxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB), and enable rapid detection of target cancer cells. Specifically, using this new assay system, clinically important breast cancer cells are detected in a 5 min time period at room temperature with high specificity and sensitivity. The remarkably high capability to catalyze oxidation reactions could allow the nanohybrid to replace conventional peroxidase-based immunoassay systems as part of new, rapid, robust and convenient assay systems which can be widely utilized for the identification of important target molecules.

We have developed multifunctional fluorescent surface enhanced Raman spectroscopic tagging material (F-SERS dots) composed of silver nanoparticle-embedded silica spheres with fluorescent organic dye and specific Raman labels for multiplex targeting, tracking, and imaging of cellular/molecular events in the living organism. In this study, F-SERS dots fabricated with specific target antibodies (BAX and BAD) were employed for the detection of apoptosis. The F-SERS dots did not show any particular toxicity in several cell lines. The F-SERS dots could monitor the apoptosis effectively and simultaneously through fluorescent images as well as Raman signals in both cells and tissues with high selectivity. Our results clearly demonstrate that F-SERS dots can be easily applicable to multiplex analysis of diverse cellular/molecular events important for maintaining cellular homeostasis.