RESUMO
Neoadjuvant chemotherapy is an alternative treatment modality for tumors. Methotrexate (MTX) has been often used as a neoadjuvant chemotherapy reagent for osteosarcoma surgery. However, the large dosage, high toxicity, strong drug resistance, and poor improvement of bone erosion restricted the utilization of methotrexate. Here, we developed a targeted drug delivery system using nanosized hydroxyapatite particles (nHA) as the cores. MTX was conjugated to polyethylene glycol (PEG) through the pH-sensitive ester linkage and acted as both the folate receptor-targeting ligand and the anti-cancer drug due to the similarity to the structure of folic acid. Meanwhile, nHA could increase the concentration of calcium ions after being uptake by cells, thus inducing mitochondrial apoptosis and improving the efficacy of medical treatment. In vitro drug release studies of MTX-PEG-nHA in phosphate buffered saline at different pH values (5, 6.4 and 7.4) indicated that the system showed a pH-dependent release feature because of the dissolution of ester bonds and nHA under acidic conditions. Furthermore, the treatment on osteosarcoma cells (143B, MG63, and HOS) by using MTX-PEG-nHA was demonstrated to exhibit higher therapeutic efficacy. Therefore, the developed platform possesses the great potential for osteosarcoma therapy.
RESUMO
This work reported an electrochemical method for the detection of SARS-CoV-2 major protease (Mpro). Specifically, ferrocene (Fc)-labeled peptide substrates were immobilized on the gold nanoparticles (AuNPs)-modified electrode. Cleavage of the peptides by Mpro led to the release of Fc tags and the decrease of the electrochemical signals. The analytical performance of the biosensor for analysis of Mpro was investigated. Inhibiting the activity of Mpro prevented the cleavage of the peptide substrates. The method was successfully used to evaluate the inhibition efficiency of a well-known inhibitor.
RESUMO
Voltammetry has been shown to be especially useful to detect epinephrine in the nervous or pharmacological system. A major limitation of this strategy, however, is the interference of ascorbic acid, which is usually present in high concentration and can be oxidized at a potential close to that of epinephrine. Furthermore, the sensitivity is rather low. In order to get selective and sensitive measurements of epinephrine in the presence of ascorbic acid via electrochemical methods, we fabricated the CNT/Nafion composite electrode and investigated the electrocatalytic activity of the composite electrode toward epinephrine in this paper. Due to the high electrocatalytic activity of CNTs and the selective penetration of Nafion membrane, the composite electrode was found to enhance the oxidation peak current and lower the overpotential of epinephrine. In the complex sample medium, permeation of the positive charged epinephrine into the electrode surface was significantly facilitated, while that of neutral ascorbic acid (AA) moiety in the acidic solution was largely blocked. As a result, interference from the coexisted ascorbic acid was excluded at the CNT/Nafion composite electrode. Differential pulse voltammetry was successfully utilized for the determination of epinephrine in the presence of a large quantity of ascorbic acid. In the presence of 4.0 mM ascorbic acid, the anodic currents of epinephrine are linearly dependent on the concentrations of epinephrine in the range of 0.2 to 20 microM with the detection limit of 0.04 microM. The feasibility of the composite electrode for determination of epinephrine in adrenaline hydrochloride injection has also been demonstrated.
