Renal clearable catalytic gold nanoclusters for in vivo disease monitoring

Ultra-small gold nanoclusters (AuNCs) have emerged as agile probes for in vivo imaging, as they exhibit exceptional tumour accumulation and efficient renal clearance properties. However, their intrinsic catalytic activity, which can enable increased detection sensitivity, has yet to be explored for in vivo sensing. By exploiting the peroxidase-mimicking activity of AuNCs and the precise nanometer size filtration of the kidney, we designed multifunctional protease nanosensors that respond to disease microenvironments to produce a direct colorimetric urinary readout of disease state in less than 1 h. We monitored the catalytic activity of AuNCs in collected urine of a mouse model of colorectal cancer where tumour-bearing mice showed a 13-fold increase in colorimetric signal compared to healthy mice. Nanosensors were eliminated completely through hepatic and renal excretion within 4 weeks after injection with no evidence of toxicity. We envision that this modular approach will enable rapid detection of a diverse range of diseases by exploiting their specific enzymatic signatures

Expanding the design space of gel materials through ionic liquid mediated mechanical and structural tuneability

Ionogels are an emerging class of soft material with exceptional properties stemming from high ionic liquid content. In contrast to other gel systems, the ionic liquid component provides an extra level of design. However, this highly modular nature has yet to be fully explored and the role ionic liquids play in the structural properties of gel-based materials is poorly understood. Here, methodical small angle neutron scattering and X-ray photoelectron spectroscopy studies reveal the relationship between bulk structure and surface composition of a soft material for the first time. Furthermore, we show how ionic liquid design dictates polymer structure, which in turn can be harnessed to fine tune the mechanical properties of ionogels. With a level of control over gel structure beyond what is possible using molecular solvents, our systematic study thus provides insight into how ionic liquids can expand the design space for gel development for a broad range of applications

Platinum nanocatalyst amplification: redefining the gold standard for lateral flow immunoassays with ultra-broad dynamic range

Paper-based lateral flow immunoassays (LFIAs) are one of the most widely used point-of-care (PoC) devices; however, their application in early disease diagnostics is often limited due to insufficient sensitivity for the requisite sample sizes and the short time frames of PoC testing. To address this, we developed a serum-stable, nanoparticle catalyst-labeled LFIA with a sensitivity surpassing that of both current commercial and published sensitivities for paper-based detection of p24, one of the earliest and most conserved biomarkers of HIV. We report the synthesis and characterization of porous platinum core–shell nanocatalysts (PtNCs), which show high catalytic activity when exposed to complex human blood serum samples. We explored the application of antibody-functionalized PtNCs with strategically and orthogonally modified nanobodies with high affinity and specificity toward p24 and established the key larger nanoparticle size regimes needed for efficient amplification and performance in LFIA. Harnessing the catalytic amplification of PtNCs enabled naked-eye detection of p24 spiked into sera in the low femtomolar range (ca. 0.8 pg·mL–1) and the detection of acute-phase HIV in clinical human plasma samples in under 20 min. This provides a versatile absorbance-based and rapid LFIA with sensitivity capable of significantly reducing the HIV acute phase detection window. This diagnostic may be readily adapted for detection of other biomolecules as an ultrasensitive screening tool for infectious and noncommunicable diseases and can be capitalized upon in PoC settings for early disease detection