Paper-based sensors for bacteria detection.

The detection of pathogenic bacteria is essential to prevent and treat infections and to provide food security. Current gold-standard detection techniques, such as culture-based assays and polymerase chain reaction, are time-consuming and require centralized laboratories. Therefore, efforts have focused on developing point-of-care devices that are fast, cheap, portable and do not require specialized training. Paper-based analytical devices meet these criteria and are particularly suitable to deployment in low-resource settings. In this Review, we highlight paper-based analytical devices with substantial point-of-care applicability for bacteria detection and discuss challenges and opportunities for future development.

Polymeric Amines Induce Nitric Oxide Release from S-Nitrosothiols.

Catalytic generation of nitric oxide (NO) from NO donors by nanomaterials has enabled prolonged NO delivery for various biomedical applications, but this approach requires laborious synthesis routes. In this study, a new class of materials, that is, polymeric amines including polyethyleneimine (PEI), poly-L-lysine, and poly(allylamine hydrochloride), is discovered to induce NO generation from S-nitrosothiols (RSNOs) at physiological conditions. Controlled NO generation can be readily achieved by tuning the concentration of the NO donors (RSNOs) and polymers, and the type and molecular weight of the polymers. Importantly, the mechanism of NO generation by these polymers is deciphered to be attributed to the nucleophilic reaction between primary amines on polymers and the SNO groups of RSNOs. The NO-releasing feature of the polymers can be integrated into a suite of materials, for example, simply by embedding PEI into poly(vinyl alcohol) (PVA) hydrogels. The functionality of the PVA/PEI hydrogels is demonstrated for Pseudomonas aeruginosa biofilm prevention with a ≈4 log reduction within 6 h. As NO has potential therapeutic implications in various diseases, the identification of polymeric amines to induce NO release will open new opportunities in NO-generating biomaterials for antibacterial, antiviral, anticancer, antithrombotic, and wound healing applications.

Sensitivity and Selectivity Analysis of Fluorescent Probes for Hydrogen Sulfide Detection.

Hydrogen sulfide (H2 S) is a gasotransmitter known to regulate physiological and pathological processes. Abnormal H2 S levels have been associated with a range of conditions, including Parkinson's and Alzheimer's diseases, cardiovascular and renal diseases, bacterial and viral infections, as well as cancer. Therefore, fast and sensitive H2 S detection is of significant clinical importance. Fluorescent H2 S probes hold great potential among the currently developed detection methods because of their high sensitivity, selectivity, and biocompatibility. However, many proposed probes do not provide a gold standard for proper use and selection. Consequently, issues arise when applying the probes in different conditions. Therefore, we systematically evaluated four commercially available probes (WSP-1, WSP-5, CAY, and P3), considering their detection range, sensitivity, selectivity, and performance in different environments. Furthermore, their capacity for endogenous H2 S imaging in live cells was demonstrated.

Ceria Nanoparticles as an Unexpected Catalyst to Generate Nitric Oxide from S-Nitrosoglutathione.

Ceria nanoparticles (NPs) are widely reported to scavenge nitric oxide (NO) radicals. This study reveals evidence that an opposite effect of ceria NPs exists, that is, to induce NO generation. Herein, S-nitrosoglutathione (GSNO), one of the most biologically abundant NO donors, is catalytically decomposed by ceria NPs to produce NO. Ceria NPs maintain a high NO release recovery rate and retain their crystalline structure for at least 4 weeks. Importantly, the mechanism of this newly discovered NO generation capability of ceria NPs from GSNO is deciphered to be attributed to the oxidation of Ce3+ to Ce4+ on their surface, which is supported by X-ray photoelectron spectroscopy and density functional theory analysis. The prospective therapeutic effect of NO-generating ceria NPs is evaluated by the suppression of cancer cells, displaying a significant reduction of 93% in cell viability. Overall, this report is, to the authors' knowledge, the first study to identify the capability of ceria NPs to induce NO generation from GSNO, which overturns the conventional concept of them acting solely as a NO-scavenging agent. This study will deepen our knowledge about the therapeutic effects of ceria NPs and open a new route toward the NO-generating systems for biomedical applications.

Modulating nitric oxide-generating activity of zinc oxide by morphology control and surface modification.

Zinc oxide (ZnO) has emerged as a promising material for nitric oxide (NO) delivery owing to its intrinsic enzyme-mimicking activities to catalyze NO prodrugs S-nitrosoglutathione (GSNO) and ß-gal-NONOate for NO generation. The catalytic performance of enzyme mimics is strongly dependent on their size, shape, and surface chemistry; however, no studies have evaluated the influence of the aforementioned factors on the NO-generating activity of ZnO. Understanding these factors will provide an opportunity to tune NO generation profiles to accommodate diverse biomedical applications. In this paper, for the first time, we demonstrate that the activity of ZnO towards catalytic NO generation is shape-dependent, resulting from the different crystal growth directions of these particles. We modified the surfaces of ZnO particles with zeolitic imidazolate framework (ZIF-8) by in situ synthesis and observed that ZnO/ZIF-8 retained 60% of its NO-generating potency. The newly formed ZnO/ZIF-8 particles were shown to catalytically decompose both endogenous (GSNO) and exogenous (ß-gal-NONOate and S-nitroso-N-acetylpenicillamine (SNAP)) prodrugs to generate NO at physiological conditions. In addition, we design the first platform that combines NO-generating and superoxide radical scavenging properties by encapsulating a natural enzyme, superoxidase dismutase (SOD), into ZnO/ZIF-8 particles, which holds great promise towards combinatorial therapy.

Metal-organic frameworks for therapeutic gas delivery.

Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) are gaseous signaling molecules (gasotransmitters) that regulate both physiological and pathological processes and offer therapeutic potential for the treatment of many diseases, such as cancer, cardiovascular disease, renal disease, bacterial and viral infections. However, the inherent labile nature of therapeutic gases results in difficulties in direct gases administration and their controlled delivery at clinically relevant ranges. Metal-organic frameworks (MOFs) with highly porous, stable, and easy-to-tailor properties have shown promising therapeutic gas delivery potential. Herein, we highlight the recent advances of MOF-based platforms for therapeutic gas delivery, either by endogenous (i.e., direct transfer of gases to targets) or exogenous (i.e., stimulating triggered release of gases) means. Reports that involve in vitro and/or in vivo studies are highlighted due to their high potential for clinical translation. Current challenges for clinical requirements and possible future innovative designs to meet variable healthcare needs are discussed.

Copper-doped metal-organic frameworks for the controlled generation of nitric oxide from endogenous S-nitrosothiols.

Nitric oxide (NO) is an essential signaling molecule with a number of biological functions and holds great promise in biomedical applications. However, NO delivery technologies have been complicated due to the inherent properties of NO which include short half-life and limited transport distance in human tissues. In addition, the biofunctionality of NO is strongly dependent on its concentrations and locations where it is delivered. To achieve controlled NO delivery, many studies have focused on encapsulating NO donors into macromolecular scaffolds or using catalysts to realize in situ NO generation from NO prodrugs. Successful applications have been shown, however NO donor-loaded platforms experience the limitation of finite NO storage capacity. The present study reports the synthesis of a catalyst, copper-doped zeolitic imidazolate framework ZIF-8 (Cu2+/ZIF-8), that is designed to generate NO from naturally occurring endogenous NO donors. By tuning the copper doping percentages, we achieved controlled NO generation from S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO). Cu2+/ZIF-8 particles retained their catalytic potency after 5 NO generation cycles and we showed that our copper-doped ZIF-8 catalyst produced a 10-fold increased amount of NO compared with previous reports. As a proof-of-concept study, we demonstrated the ability of copper-doped ZIF-8 to disperse bacterial biofilms in the presence of GSNO.

DNA-mediated anisotropic silica coating of upconversion nanoparticles.

We report a facile approach of using DNA molecules as switches to selectively activate silica coating onto specific facets of upconversion nanoparticles. Being simple and reproducible, this method improves the understanding of the silica coating mechanism and opens up new opportunities for nanomedicine delivery.

Exonuclease III-Assisted Upconversion Resonance Energy Transfer in a Wash-Free Suspension DNA Assay.

Sensitivity is the key in optical detection of low-abundant analytes, such as circulating RNA or DNA. The enzyme Exonuclease III (Exo III) is a useful tool in this regard; its ability to recycle target DNA molecules results in markedly improved detection sensitivity. Lower limits of detection may be further achieved if the detection background of autofluorescence can be removed. Here we report an ultrasensitive and specific method to quantify trace amounts of DNA analytes in a wash-free suspension assay. In the presence of target DNA, the Exo III recycles the target DNA by selectively digesting the dye-tagged sequence-matched probe DNA strand only, so that the amount of free dye removed from the probe DNA is proportional to the number of target DNAs. Remaining intact probe DNAs are then bound onto upconversion nanoparticles (energy donor), which allows for upconversion luminescence resonance energy transfer (LRET) that can be used to quantify the difference between the free dye and tagged dye (energy acceptor). This scheme simply avoids both autofluorescence under infrared excitation and many tedious washing steps, as the free dye molecules are physically located away from the nanoparticle surface, and as such they remain "dark" in suspension. Compared to alternative approaches requiring enzyme-assisted amplification on the nanoparticle surface, introduction of probe DNAs onto nanoparticles only after DNA hybridization and signal amplification steps effectively avoids steric hindrance. Via this approach, we have achieved a detection limit of 15 pM in LRET assays of human immunodeficiency viral DNA.