Extremely small-sized globular poly(ethylene glycol)-cyclic RGD conjugates targeting integrin αvß3 in tumor cells.

In this study, we report an extremely small-sized globular poly(ethylene glycol) (gPEG) conjugated with cyclic arginine-glycine-aspartic acid (cRGD) peptide and chlorin e6 (Ce6). This nanoparticle design takes advantage of the biocompatible functional gPEG (3-4nm in diameter) as an extremely small-sized drug carrier, the tumor targeting ability of cRGD, and the photodynamic tumor ablation ability of Ce6. We found that gPEG conjugated with cRGD and Ce6 (cRGD-gPEG-Ce6) exhibited much higher phototoxicity in SKOV-3 tumor cells (which have a very high density of integrin αvß3 receptors) than in KB cells (which have a very low density of integrin αvß3 receptors). Accordingly, cRGD-gPEG-Ce6 treatment resulted in a significant regression of in vivo SKOV-3 tumors, highlighting the potential of an extremely small-sized drug carrier platform for site-specific receptor-mediated tumor therapy.

A highly sensitive and selective impedimetric aptasensor for interleukin-17 receptor A.

Interleukin-17 receptor A (IL-17RA) has been recognized as a valuable biomarker for diverse diseases, including autoimmune diseases. In this work, an electrochemical biosensor with great sensitivity and selectivity toward IL-17RA was fabricated using an IL-17RA aptamer (Kd=14.00nM) for the first time. The aptasensor was manufactured using electrodeposition of gold nanoparticles, and then quantitative detection of IL-17RA was performed based on impedimetry. The developed sensor exhibited a superior analytical performance for IL-17RA with a wide dynamic range of 10-10,000pg/mL in buffer and a detection limit of 2.13pg/mL, which is lower than that of commercially available ELISA kits. In addition, we validated the high specificity of the designed aptasensor to only IL-17RA, which showed good sensitivity even in human serum solution. Furthermore, the detection of the differentiated HL-60 cells expressing IL-17RA was successfully performed. Clinical applicability of the sensor was also demonstrated utilizing neutrophils separated from asthma patients. It is expected that the fabricated aptasensor will become an excellent diagnostic platform for IL-17RA-mediated diseases.

Electrochemical aptasensor of cardiac troponin I for the early diagnosis of acute myocardial infarction.

Cardiac troponin I (cTnI) is well-known as a promising biomarker for the early diagnosis of acute myocardial infarction (AMI). In this work, single-stranded DNA aptamers against cTnI were identified by the Systematic Evolution of Ligands by Exponential enrichment (SELEX) method. The aptamer candidates exhibited a high selectivity and sensitivity toward both cTnI and the cardiac Troponin complex. The binding affinities of each aptamer were evaluated based on their dissociation constants (Kd) by surface plasma resonance. The Tro4 aptamer that had the highest binding capacity to cTnI showed a very low Kd value (270 pM) compared with that of a cTnI antibody (20.8 nM). Furthermore, we designed a new electrochemical aptasensor based on square wave voltammetry using ferrocene-modified silica nanoparticles. The developed aptasensor demonstrated an excellent analytical performance for cTnI with a wide linear range of 1-10 000 pM in a buffer and a detection limit of 1.0 pM (24 pg/mL; S/N = 3), which was noticeably lower than the cutoff values (70-400 pg/mL). The specificity of the aptamers was also examined using nontarget proteins, demonstrating that the proposed sensor responded to only cTnI. In addition, cTnI was successfully detected in a human serum albumin solution. On the basis of the calibration curve that was constructed, the concentrations of cTnI in a solution supplemented with human serum were effectively measured. The calculated values correlated well with the actual concentrations of cTnI. It is anticipated that the highly sensitive and selective aptasensor for cTnI could be readily applicable for the accurate diagnosis of AMI.