Noninvasive monitoring of hepatic glutathione depletion through fluorescence imaging and blood testing.

Hepatic glutathione plays a key role in regulating redox potential of the entire body, and its depletion is known to increase susceptibility to oxidative stress involved in many diseases. However, this crucial pathophysiological event can only be detected noninvasively with high-end instrumentation or invasively with surgical biopsy, limiting both preclinical research and clinical prevention of oxidative stress-related diseases. Here, we report that both in vivo fluorescence imaging and blood testing (the first-line detection in the clinics) can be used for noninvasive and consecutive monitoring of hepatic glutathione depletion at high specificity and accuracy with assistance of a body-clearable nanoprobe, of which emission and surface chemistries are selectively activated and transformed by hepatic glutathione in the liver sinusoids. These findings open a new avenue to designing exogenous blood markers that can carry information of local disease through specific nanobiochemical interactions back to the bloodstream for facile and rapid disease detection.

A Cut-Resistant and Highly Restorable Graphene Foam.

High-pressure resistant and multidirectional compressible materials enable various applications but are often hindered by structure-derived collapse and weak elasticity. Here, a super-robust graphene foam with ladder shape microstructure capable of withstanding high pressure is presented. The multioriented ladder arrays architecture of the foam, consisting of thousands of identically sized square spaces, endow it with a great deal of elastic units. It can easily bear an iterative and multidirectional pressure of 44.5 MPa produced by a sharp blade, and may completely recover to its initial state by a load of 180 000 times their own weight even under 95% strain. More importantly, the foam can also maintain structural integrity after experiencing a pressure of 2.8 GPa through siphoning. Computational modeling of the "buckling of shells" mechanism reveals the unique ladder-shaped graphene foam contributes to the superior cut resistance and good resilience. Based on this finding, it can be widely used in cutting resistance sensors, monitoring of sea level, and the detection of oily contaminants in water delivery pipelines.

Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non-human Primates.

While dose dependencies in pharmacokinetics and clearance are often observed in clinically used small molecules, very few studies have been dedicated to the understandings of potential dose-dependent in vivo transport of nanomedicines. Here we report that the pharmacokinetics and clearance of renal clearable gold nanoparticles (GS-AuNPs) are strongly dose-dependent once injection doses are above 15 mg kg-1 : high dose expedited the renal excretion and shortened the blood retention. As a result, the no-observed-adverse-effect-level (NOAEL) of GS-AuNPs was >1000 mg kg-1 in CD-1 mice. The efficient renal clearance and high compatibility can be translated to the non-human primates: no adverse effects were observed within 90 days after intravenous injection of 250 mg kg-1 GS-AuNPs. These fundamental understandings of dose effect on the in vivo transport of ultrasmall AuNPs open up a pathway to maximize their biomedical potentials and minimize their toxicity in the future clinical translation.

Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime.

The glomerular filtration barrier is known as a 'size cutoff' slit, which retains nanoparticles or proteins larger than 6-8 nm in the body and rapidly excretes smaller ones through the kidneys. However, in the sub-nanometre size regime, we have found that this barrier behaves as an atomically precise 'bandpass' filter to significantly slow down renal clearance of few-atom gold nanoclusters (AuNCs) with the same surface ligands but different sizes (Au18, Au15 and Au10-11). Compared to Au25 (∼1.0 nm), just few-atom decreases in size result in four- to ninefold reductions in renal clearance efficiency in the early elimination stage, because the smaller AuNCs are more readily trapped by the glomerular glycocalyx than larger ones. This unique in vivo nano-bio interaction in the sub-nanometre regime also slows down the extravasation of sub-nanometre AuNCs from normal blood vessels and enhances their passive targeting to cancerous tissues through an enhanced permeability and retention effect. This discovery highlights the size precision in the body's response to nanoparticles and opens a new pathway to develop nanomedicines for many diseases associated with glycocalyx dysfunction.

Superelastic, Macroporous Polystyrene-Mediated Graphene Aerogels for Active Pressure Sensing.

Three-dimensional (3D) graphene-based polymer/graphene aerogels with excellent mechanical properties are crucial for broad applications. The creation of such polymer/graphene aerogels remains challenging because of the poor dispersion and compatibility of polymer within the graphene matrix. By using the freezing-directed assembly of graphene under the assistance of surfactant, 3D macroporous polystyrene/graphene aerogels (MPS-GAs) with lightweight, superelastivity (80 % strain), high strength (80 kPa), and good electrical properties have been achieved in this study. The as-prepared MPS-GAs shows excellent electromechanical performance with stable cyclic resilient properties and sensitive resistance responses, thus making the MPS-GAs promising candidates for applications in actuators, elastic conductors, strain/pressure sensors, and wearable devices.