Development of enzyme-inorganic hybrid nanoflower-modified electrodes and a smartphone-controlled electrochemical analyzer for point-of-care testing of salivary amylase in saliva.

Quantitation of salivary alpha-amylase (sAA) plays a significant role in not only theoretical studies but also clinical practice. This study reports a quantitative point-of-care testing (POCT) system for sAA quantitation anywhere, anytime and by anyone, which consists of customized electrodes and a smartphone-controlled electrochemical analyzer. Organic-inorganic hybrid nanoflowers (NFs) encapsulating α-glucosidase (AG) and glucose dehydrogenase (GDH) have been synthesized and modified onto screen-printed electrodes (SPCEs) to fabricate the customized electrodes. The SPCEs integrated with the smartphone-controlled electrochemical analyzer exhibit good analytical performance for sAA with a low detection limit of 5.02 U mL-1 and a wide dynamic range of 100-2000 U mL-1 using chronoamperometry. The reported POCT system has been successfully demonstrated for quantitation of sAA in clinical saliva samples, and the quantitation results correlated well with those of the Bernfeld method which is extensively used in clinics. More importantly, this study reveals the great potential of sAA as an early warning indicator of abnormal glucose metabolism in obese individuals. Considering the non-invasive saliva sampling process as well as the easy-to-use and cost-effectiveness features of this quantitative POCT system, quantitation of salivary sAA at home by laypersons might become an appealing choice for obese individuals to monitor their glucose metabolism status anytime.

An MMP-2 Responsive Nanotheranostic Probe Enabled Synergistic Therapy of Rheumatoid Arthritis and MR/CT Assessment of Therapeutic Response In Situ.

This study reports a facile and green synthesis of a new multifunctional nanotheranostic probe for the synergistic therapy of rheumatoid arthritis (RA) and in situ assessment of therapeutic response. The probe is synthesized through a one-step self-assembly of two exquisitely designed peptide-amphiphilic block copolymers (PEG-DTIPA-KGPLGVRK-MTX and Pal-GGGGHHHHD-TCZ) under mild conditions, requiring minimal energy input. The resultant probe demonstrates excellent biocompatibility, water solubility, and colloidal stability. It exhibits a strong IL-6R targeting ability toward inflamed joints, and releases drugs in an MMP-2-responsive manner. The co-loading of methotrexate(MTX) and tocilizumab (TCZ) into the probe enables synergistic RA therapy with improved efficacy by simultaneously decreasing the activity of adenosine synthetase and interfering with the binding of IL-6 to its receptor. In addition, the resultant probe exhibits a high r1 relaxation rate (7.00 mm-1  s-1 ) and X-ray absorption capability (69.04 Hu mm-1 ), enabling sensitive MR and CT dual-modal imaging for simultaneous evaluation of synovial thickness and bone erosion. Both in vitro experiments using lipopolysaccharide-treated RAW264.7 cells and in vivo experiments using collagen-induced arthritis mice demonstrate the probe's high effectiveness in synergistically inhibiting inflammation. This study provides new insights into RA theranostics, therapeutic monitoring, the design of multifunctional theranostic probes, and beyond.

A smartphone-based fluorospectrophotometer and ratiometric fluorescence nanoprobe for on-site quantitation of pesticide residue.

Cost-effective and user-friendly quantitation at points-of-need plays an important role in food safety inspection, environmental monitoring, and biomedical analysis. This study reports a stand-alone smartphone-based fluorospectrophotometer (the SBS) installed with a custom-designed application (the SBS-App) for on-site quantitation of pesticide using a ratiometric sensing scheme. The SBS can collect fluorescence emission spectra in the wavelength range of 380-760 nm within 5 s. A ratiometric fluorescence probe is facilely prepared by directly mixing the blue-emissive carbon nanodots (the Fe3+-specific fluorometric indicator) and red-emissive quantum dots (the internal standard) at a ratio of 11.6 (w/w). Based on the acetylcholinesterase/choline oxidase dual enzyme-mediated cascade catalytic reactions of Fe2+/Fe3+ transformation, a ratiometric fluorescence sensing scheme is developed. The practicability of the SBS is validated by on-site quantitation of chlorpyrifos in apple and cabbage with a comparable accuracy to the GC-MS method, offering a scalable solution to establish a cost-effective surveillance system for pesticide pollution.

BSA-templated synthesis of Ir/Gd bimetallic oxide nanotheranostics for MR/CT imaging-guided photothermal and photodynamic synergistic therapy.

Precision medicine urges the development of theranostics which can efficiently integrate precise diagnosis and effective therapy. In this study, a facile synthesis of Ir/Gd bimetallic oxide nanotheranostics (termed BSA@Gd2O3/IrO2 NPs) with good biocompatibility was demonstrated using a biomineralization method where bovine serum albumin (BSA) served as a versatile template. BSA@Gd2O3/IrO2 NPs exhibited high longitudinal relaxivity (5.2 mM-1 s-1) and X-ray absorption capability (14.5 Hu mM-1), illustrating them to be a good contrast agent for magnetic resonance (MR) and computed tomography (CT) dual-modal imaging. Moreover, BSA@Gd2O3/IrO2 NPs can act as not only a photothermal conversion agent with ultrahigh efficiency (66.7%) as well as a good photosensitizer, but also an effective catalase to decompose endogenous H2O2 to produce O2, thus relieving hypoxia and enhancing the phototherapeutic effect. Both in vitro and in vivo experiments demonstrated the high effectiveness of BSA@Gd2O3/IrO2 NPs in MR/CT dual-modal imaging and photothermal and photodynamic synergistic tumor treatments. This work sheds new light on the development of versatile nanotheranostic systems using mild and robust biomineralization methods.