Abstract Anti-mullerian hormone (AMH) detection receives much attention since it is used as an ideal biomarker for quantitative assessment of ovarian reserve. The present study proposed a first report on the use of MOF-on-MOF as an electrochemical sensor for recognizing AMH in buffer and serum media. The MOF-on-MOF, MIL-88 B@UiO66NH2 was synthesized by the internal extended growth method (IEGM) involving MIL-88 B on UiO66NH2 by in situ method for the first time. MOF matrix could be established to form a three-dimensional (3D) core-shell hybrid unit using MOFs with distinct characteristics. The morphology, structural characteristics, and electrochemical performance of MIL-88 B@UiO66NH2 were studied. It was successfully used for AMH sensing to demonstrate the detection performance of the internal extended growth method (IEGM) grown MIL-88 B@UiO66NH2 made immunosensor. The electrochemical results indicated that MOF-on-MOF exhibited linear EIS response for AMH concentration varying from 100 ng/mL to 1 fg/mL. Further, the immunosensor displayed high specificity and sensitivity for AMH detection. The fabricated sensor attained a remarkable limit of detection (LOD) of 1.07 fg/mL and 0.82 fg/mL, when studied in PBS and 10% serum buffer media, respectively. The biosensor achieved the limit of quantification (LOQ) of 3.25 fg/mL and 2.5 fg/mL, respectively, when analyzed in PBS buffer and 10% serum buffer. The significant results emphasized that the fabricated biosensor holds a promising potential to act as an appropriate tool for rapid assessment of AMH levels.
Abstract The blood-brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the inefficient release of therapeutic payload hinders their efficacy from crossing the BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engagerTfR) that can complex with PEGylated nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain microvascular endothelial cells, while rapidly dissociating from PEGylated nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to cross the BBB. The pH-PEG engagerTfR significantly increased the accumulation of PEGylated nanomedicine in the mouse brain compared to wild-type PEG engagerTfR (WT-PEG engagerTfR). pH-PEG engagerTfR-decorated PEGylated liposomal doxorubicin exhibited an enhanced antitumor effect and extended survival in a human glioblastoma (GBM) orthotopic xenograft mice model. Conditional release of PEGylated nanomedicine during BBB-related receptor-mediated transcytosis by pH- PEG engagerTfR is promising for enhanced brain drug delivery to treat CNS disorders.
Abstract Clinical diagnosis of diseases like cancer, requires rapid and ultrasensitive screening methods. β-galactosidase (β-gal) is a glycoside hydrolase enzyme, that is upregulated in senescent cells and primary ovarian cancer cells. It is considered a significant biomarker for cellular senescence and primary ovarian cancers. The current study demonstrates the designing of a bimetallic metal-organic framework, (Fe, Cu)-MOF-919, as an ultrasensitive electrochemical immunosensor for investigating ꞵ-galactosidase (β-gal) enzyme on screen-printed carbon electrodes (SPCE) using electrochemical impedance spectroscopy (EIS) in human oral cancer plasma samples. The sensor exhibited a linear response in a wide concentration of β-gal ranging from 10 fg/mL to 1 ng/mL with a limit of detection (LOD) of 4.79 fg/mL and a limit of quantification (LOQ) of 14.53 fg/mL. Furthermore, the sensor confirmed outstanding selectivity and sensitivity against biologically significant interfering molecules. Analyses of β-gal in human oral cancer samples also demonstrated the potential of β-gal for clinical diagnosis. The sensing approach holds substantial clinical relevance by being a promising option for designing latent biosensors.
