Biomimetic and multifunctional nanocomposites for precision fungi theranostics.

Fungi infection is a serious threat to public health, but an effective antifungal strategy remains a challenge. Herein, a biomimetic nanocomposite with multifunctionalities, including fungi diagnosis, antifungal adhesion, precise fungi elimination, and cytokine sequestration, is constructed for battling Candida albicans (C. albicans) infection. By screening a range of cells, we find that the polarized macrophage cells have the strongest binding tendency toward C. albicans. Thus, their membranes were exfoliated to camouflage UCNPs and then decorated with photosensitizers (methylene blue, MB) and DNA sensing elements. The resulting nanocomposite can tightly bind to fungal surfaces, promote DNA recognition, and squeeze pro-inflammatory cytokines to relieve inflammation. Consequently, this nanocomposite can detect C. albicans with enhanced sensitivity and precisely eliminate fungal cells through photodynamic therapy with minimal phototoxicity because of its switchable fluorescence behavior. The developed nanocomposite with good biocompatibility achieves a satisfactory diagnostic and therapeutic effect in a C. albicans-infected mouse model, which offers a unique approach to fight fungi infection.

A smart pathogen detector engineered from intracellular hydrogelation of DNA-decorated macrophages.

Bacterial infection is a major threat to global public health, which urgently requires useful tools to rapidly analyze pathogens in the early stages of infection. Herein, we develop a smart macrophage (Mø)-based bacteria detector, which can recognize, capture, enrich and detect different bacteria and their secreted exotoxins. We transform the fragile native Møs into robust gelated cell particles (GMøs) using photo-activated crosslinking chemistry, which retains membrane integrity and recognition capacity for different microbes. Meanwhile, these GMøs equipped with magnetic nanoparticles and DNA sensing elements can not only respond to an external magnet for facile bacteria collection, but allow the detection of multiple types of bacteria in a single assay. Additionally, we design a propidium iodide-based staining assay to rapidly detect pathogen-associated exotoxins at ultralow concentrations. Overall, these nanoengineered cell particles have broad applicability in the analysis of bacteria, and could potentially be used for the management and diagnosis of infectious diseases.

Precise Molecular Profiling of Circulating Exosomes Using a Metal-Organic Framework-Based Sensing Interface and an Enzyme-Based Electrochemical Logic Platform.

Exosomes have emerged as a promising circulating tumor biomarker; however, it is a big challenge for convenient, multiparametric, and accurate profiling of tumorous exosomes due to their unique structure and heterogeneity. To address these problems, we develop a highly integrated electrochemical platform for molecular profiling of tumor exosomes. A metal-organic framework-functionalized sensing interface is fabricated through a simple self-growth process, which collects exosomes from biofluids without additional separation steps. Meanwhile, a sensing strategy is designed to analyze both exosomal protein and RNA markers on a single chip based on the unique sensor architecture, allowing detection of low-abundance targets (∼250 vesicles in a 10 µL sample) using an integrated microfluidic electrochemical device. Furthermore, a multiple-input, protein enzyme-based logic gate is introduced into the system to accurately identify breast cancer patients with 100% sensitivity and specificity, thus revealing the advantageous role of logical profiling of exosomes in early diagnostics of tumor.