Bimetallic Nanozyme: A Credible Tag for In Situ-Catalyzed Reporter Deposition in the Lateral Flow Immunoassay for Ultrasensitive Cancer Diagnosis.

The lateral flow immunoassay (LFIA) is a sought-after point-of-care testing platform, yet the insufficient sensitivity of the LFIA limits its application in the detection of tumor biomarkers. Here, a colorimetric signal amplification method, bimetallic nanozyme-mediated in situ-catalyzed reporter deposition (BN-ISCRD), was designed for ultrasensitive cancer diagnosis. The bimetallic nanozyme used, palladium@iridium core-shell nanoparticles (Pd@Ir NPs), had ultrahigh enzyme-like activity, which was further explained by the electron transfer of Pd@Ir NPs and the change in the Gibbs free energy during catalysis through density functional theory calculations. With gastric cancer biomarkers pepsinogen I and pepsinogen II as model targets, this assay could achieve a cutoff value of 10 pg/mL, which was 200-fold lower than that without signal enhancement. The assay was applied to correctly identify 8 positive and 28 negative clinical samples. Overall, this BN-ISCRD-based LFIA showed great merits and potential in the application of ultrasensitive disease diagnosis.

A Universal Bacterial Catcher Au-PMBA-Nanocrab-Based Lateral Flow Immunoassay for Rapid Pathogens Detection.

In traditional lateral flow immunoassays (LFIA) for pathogens detection, capture antibody (CA) is necessary and usually conjugated to Au nanoparticles (NPs) in order to label the target analyte. However, the acquisition process of the Au-CA nanoprobe is relatively complicated and costly, which will limit the application of LFIA. Herein, p-mercaptophenylboronic acid-modified Au NPs (namely Au-PMBA nanocrabs), were synthesized and applied for a new CA-independent LFIA method. The stable Au-PMBA nanocrabs showed outstanding capability to capture both Gram-negative bacteria and Gram-positive bacteria through covalent bonding. The acquired Au-PMBA-bacteria complexes were dropped onto the strip, and then captured by the detection antibody on the test line (T-line). Take Escherichia coli O157:H7 as an example, the gray value of T-line was proportional to the bacteria concentration and the linear range was 103-107 cfu·mL-1. This CA-independent strategy exhibited higher sensitivity than the traditional CA-dependent double antibody sandwich method, because detection limit of the former one was 103 cfu·mL-1 only by visual observation, which was reduced by 3 orders of magnitude. Besides, this platform successfully screened E. coli O157:H7 in four food samples with recoveries ranging from 90.25% to 107.25%. This CA-independent LFIA showed great advantages and satisfactory potential for rapid foodborne pathogens detection in real samples.

A universal boronate affinity capture-antibody-independent lateral flow immunoassay for point-of-care glycoprotein detection.

Protein glycosylation and other post-translational modifications are involved in many biological processes including growth, development and immune responses, and glycoproteins are also known as biomarkers for cancer, diabetes and cardiovascular diseases. In traditional lateral flow immunoassay (LFIA) for glycoprotein detection, capture antibody (CA) is often required to label targets. However, the production of CA is complicated and expensive, restricting the wide application of LFIA. In this study, we developed a universal boronate affinity CA-independent LFIA method for glycoprotein detection. 4-Mercaptophenylboronic acid (4-MPBA)-modified Au nanoparticles (namely 4-MPBA-AuNPs) were used as LFIA labels, which could generate colorimetric signal and showed outstanding capability to bind glycoprotein. Compared with CA, 4-MPBA molecular as a glycoprotein recognition element had more prominent advantages, e.g., low cost, easy availability and good quality controllability. Take carcinoembryonic antigen (CEA) as model glycoprotein, the limit of detection of this CA-independent LFIA was 1.25 ng/mL by naked eyes, which was 8-fold lower than conventional CA-dependent sandwich LFIA. Significantly, the developed 4-MPBA-AuNPs-based CA-independent LFIA successfully detected 23 CEA-positive samples from 64 suspected human serum samples within 50 min in a nonlaboratory environment, with a 100% accuracy compared to clinical detection method. Therefore, this diagnostic platform could provide an effective tool for point-of-care glycoprotein detection with excellent reproducibility and high specificity.

A Novel Methacryloyl Chitosan Hydrogel Microneedles Patch with Sustainable Drug Release Property for Effective Treatment of Psoriasis.

Psoriasis is a chronic and recurrent skin disease that often requires long-term treatment, and topical transdermal drug delivery can reduce systemic side effects. However, it is still a challenge in efficient transdermal drug delivery for psoriasis treatment due to low penetration efficiency of most drugs and the abnormal skin conditions of psoriasis patients. Here, a safe and effective methacryloyl chitosan hydrogel microneedles (CSMA hMNs) patch is developed and served as a sustained drug release platform for the treatment of psoriasis. By systematically optimizing the CSMA preparation, CSMA hMNs with excellent morphological characteristics and strong mechanical properties (0.7 N needle-1 ) are prepared with a concentration of only 3% (w/v) CSMA. As a proof-of-concept, methotrexate (MTX) and nicotinamide (NIC) are loaded into CSMA hMNs patch, which can produce a sustained drug release of 80% within 24 h in vitro. In vivo experiments demonstrated that the CSMA hMNs patch can effectively inhibit the skin thickening and spleen enlargement of psoriatic mice and has a good biosafety profile at sufficient therapeutic doses. This study provides a new idea for the preparation of hMN systems using modified CS or other biocompatible materials and offers an effective therapeutic option for psoriasis treatment.