A Size-Selectively Biomolecule-Immobilized Nanoprobe-Based Chemiluminescent Lateral Flow Immunoassay for Detection of Avian-Origin Viruses.

In this study, a signal-amplifiable nanoprobe-based chemiluminescent lateral flow immunoassay (CL-LFA) was developed to detect avian influenza viruses (AIV) and other contagious and fatal viral avian-origin diseases worldwide. Signal-amplifiable nanoprobes are capable of size-selective immobilization of antibodies (binding receptors) and enzymes (signal transducers) on sensitive paper-based sensor platforms. Particle structure designs and conjugation pathways conducive for antigen accessibility to maximum amounts of immobilized enzymes and antibodies have advanced. The detection limit of the CL-LFA using the signal-amplifiable nanoprobe for the nucleoprotein of the H3N2 virus was 5 pM. Sensitivity tests for low pathogenicity avian influenza H9N2, H1N1, and high pathogenicity avian influenza H5N9 viruses were conducted, and the detection limits of CL-LFA were found to be 103.5 50% egg infective dose (EID50)/mL, 102.5 EID50/mL, and 104 EID50/mL, respectively, which is 20 to 100 times lower than that of a commercial AIV rapid test kit. Moreover, CL-LFA demonstrated high sensitivity and specificity against 37 clinical samples. The signal-amplifiable probe designed in this study is a potential diagnostic probe with ultrahigh sensitivity for applications in the field of clinical diagnosis, which requires sensitive antigen detection as evidenced by enhanced signaling capacity and sensitivity of the LFAs.

Integrated Bioaerosol Sampling/Monitoring Platform: Field-Deployable and Rapid Detection of Airborne Viruses.

Airborne pathogens causing infectious diseases are often highly transmittable between humans. Therefore, an airborne pathogen-monitoring system capable of on-site detection and identification would aid tremendously in preventing and controlling the early stages of pathogen spread. Here, we describe an integrated sampling/monitoring platform for on-site and real-time detection of airborne viruses. We used MS2 bacteriophage and avian influenza virus (AIV) H1N1 to evaluate bioaerosol sampling and detection performance of the platform. Our results show that, within 20 min, aerosolized viruses can be detected using the signal of near-infrared (NIR)-to-NIR nanoprobes. The pretreatment of the sampling pad improved the transfer efficiency of MS2 viruses to the detection zone, compared to an untreated pad. Our platform could detect concentrations as low as 104.294 50% egg infectious dose (EID50)/m3 AIVs collected from a cloacal swab sample (104.838 EID50/mL). These results indicate that our sampling/monitoring platform could be applied for the early detection of biological hazards in various fields.

Sequential MR Image-Guided Local Immune Checkpoint Blockade Cancer Immunotherapy Using Ferumoxytol Capped Ultralarge Pore Mesoporous Silica Carriers after Standard Chemotherapy.

Herein, ferumoxytol (Fer) capped antiprogrammed cell death-ligand 1 (PD-L1) antibodies (aPD-L1) loaded ultralarge pore mesoporous silica nanoparticles (Fer-ICB-UPMSNPs) are formulated for a sequential magnetic resonance (MR) image guided local immunotherapy after cabazitaxel (Cbz) chemotherapy for the treatment of prostate cancer (PC). The highly porous framework of UPMSNP provides a large capacity for aPD-L1. Fer capping of the pores extends the period of aPD-L1 release and provides MR visibility of the aPD-L1 loaded UPMSNP. As-chosen Cbz chemotherapy prior to the local immunotherapy induces strong immunogenic cell death, dendritic cell maturation, and upregulation of PD-L1 of tumor cells. Finally, tumor growth inhibition of sequential MR image-guided local delivery of Fer-ICB-UPMSNPs and a tumor specific adoptive immune reaction are demonstrated in the pretreated Tramp C1 PC mouse model with Cbz chemotherapy. The tumor suppression is superior to those obtained with systemic ICB treatment after Cbz, only Fer-ICB-UPMSNP or only Cbz. As a proof-of concept, MR image-guided local ICB immunotherapy using Fer-ICB-UPMSNPs after chemotherapy suggests a new perspective of translational local immunotherapy for patients who are treated with standard chemotherapies.