The glomerular filtration barrier is known as a “size cut-off” slit to retain nanoparticles or proteins larger than 6~8 nm in the body, and to rapidly excrete the smaller ones through the kidneys. However, in a sub-nm size regime, we found that this barrier behaved 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 the size resulted in 4~9 times reductions in the renal clearance efficiency in the early elimination stage because the smaller AuNCs were more readily trapped by the glomerular glycocalyx than the larger ones. This unique in vivo nano-bio interaction in the sub-nm regime also slows down the extravasation of sub-nm AuNCs from normal blood vessels and enhances their passive targeting to cancerous tissues through 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.

No abstract

We used a recombinant adeno-associated virus vector (AAV) to deliver a foreign gene, green fluorescent protein (GFP), into mature neurons in adult rat CNS in vivo. Microinjections of AAV as small as 50 nl transduced hundreds of neurons at the injection site. There was virtually no retrograde transport as fewer than one neuron per brain was found distant from the injection site that exhibited GFP immunoreactivity. The gene product, GFP, filled the entire neuronal cytoplasmic compartment; GFP immunoreactivity was robust in cell bodies, axons, and nerve terminals. There was no tissue damage at the injection sites or pathogenicity indicated by changes in astrocytic or microglial markers. There was no inflammatory response as judged by leukocytic invasion. Gene expression in transduced cells was robust and apparently permanent: there was no evidence of phenotypic reversion up to 12 weeks following infection. AAV is an excellent vector for introducing foreign genes into mature CNS neurons. Not only might it be an ideal vehicle for gene therapy, but also the GFP-containing AAV presents a new strategy for tracing long axonal pathways in the CNS, which is difficult with current tracers (PHAL, biotinylated dextrans).

Edited by Tamas DalmayKeywords: miR-29a Collagen IV High glucose TGF-b1 HK-2 cell a b s t r a c t Deposition of collagen IV in proximal tubule cells (PTCs) plays an important role during diabetic nephropathy, but the mechanism underlying excessive production of collagen IV remains poorly understood. In this study, we examined the miRNA profile of HK-2 cells and found that high glucose/TGF-b1 induced significant down-regulation of miR-29a. We then showed that miR-29a negatively regulated collagen IV by directly targeting the 3 0 UTRs of col4a1 and col4a2. These results suggest that miR-29a acts as a repressor to fine-tune collagen expression and that the reduction of miR-29a caused by high glucose may increase the risk of excess collagen deposition in PTCs.

Glutathione-mediated biotransformation in the liver is a well-known detoxification process to eliminate small xenobiotics but its impacts on nanoparticle retention, targeting and clearance are much less understood than liver macrophage uptake even though both processes are involved in the liver detoxification. By designing a thiol-activatable fluorescent gold nanoprobe that can bind to serum protein and be transported to the liver, we noninvasively imaged this biotransformation kinetics in vivo at high specificity and examined this process at the chemical level. Our results show that glutathione efflux from hepatocytes resulted in high local concentrations of both glutathione and cysteine in liver sinusoids, which transformed the nanoparticle surface chemistry, reduced its affinity to serum protein and significantly altered its blood retention, targeting and clearance. With this biotransformation, liver detoxification, a long-standing barrier in nanomedicine translation, can be turned into a bridge toward maximizing targeting and minimizing nanotoxicity. Liver detoxification is a natural defense response that the body uses to remove foreign materials; however, due to rapid uptake by mononuclear phagocyte system (MPS) in the liver 1, 2, 3 , it often dramatically shortens the blood retention of engineered nanoparticles, prevents them from efficiently targeting diseases and retains them in the body for a long time, which can induce long-term nanotoxicity and hamper their clinical translation, particularly for those non-degradable ones composed of toxic elements or heavy metals 4, 5. However, liver detoxification also plays an important role in minimizing toxicities of small xenobiotics. For instance, glutathione (GSH)-mediated biotransformation is one of the most common liver detoxification strategies to eliminate lipophilic molecules and heavy metals 6. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio-nano papers, the community responds. Below we report short extracts highlighting the main messages of the correspondences we received. The interested readers can find the complete pieces in the accompanying Supplementary Information.

As a bridge between individual atoms and large plasmonic nanoparticles, ultrasmall (core size <3 nm) noble metal nanoparticles (UNMNPs) have been serving as model for us to fundamentally understand many unique properties of noble metals that can only be observed at an extremely small size scale. With decades’efforts, many significant breakthroughs in the synthesis, characterization and functionalization of UNMNPs have laid down a solid foundation for their future applications in the healthcare. In this review, we aim to tightly correlate these breakthroughs with their biomedical applications and illustrate how to utilize these breakthroughs to address long-standing challenges in the clinical translation of nanomedicines. In the end, we offer our perspective on the remaining challenges and opportunities at the frontier of biomedical-related UNMNPs research.

As a “silent killer”, kidney disease is often hardly detected at its early stage but can cause the lethal kidney failure in its late stage. Thus, a preclinical imaging technique that can readily differentiate the stages of kidney dysfunction is highly desired for fundamental understanding of kidney disease progression. Herein, we reported that in vivo fluorescence imaging, enabled by renal clearable near infrared-emitting gold nanoparticles, can noninvasively detect kidney dysfunction, report the dysfunctional stages and even reveal adaptive function in mouse model of unilateral obstructive nephropathy that cannot be diagnosed with routine kidney function markers. These results demonstrated that low-cost florescence kidney functional imaging is highly sensitive for longitudinal, noninvasive monitoring of kidney dysfunction progression in the preclinical research.