Glutathione-coated luminescent gold nanoparticles (GS-AuNPs) of ~ 2.5 nm behave like small dye molecules (IRdye 800CW) in physiological stability and renal clearance, but exhibit much longer tumor retention time and faster normal tissue clearance than the dye molecules, indicating that well-known enhanced permeability and retention (EPR) effect, a unique strength of conventional nanoparticles (NPs) in tumor targeting, still exists in such small NPs. These merits enable the AuNPs to more rapidly detect tumor than the dye molecules without severe accumulation in reticuloendothelial system (RES) organs, holding great promise in cancer diagnosis and therapy.

Got it PEGged: PEGylation and zwitterionization have distinct effects on the pharmacokinetic and tumor‐targeting properties of luminescent gold nanoparticles (AuNPs), although both strategies lead to effective renal clearance. High tumor‐targeting efficiency and specificity were obtained with PEGylated AuNPs, whereas rapid tumor detection was more readily achieved with zwitterionic AuNPs. HD=hydrodynamic diameter, GS=glutathione.

Size-independent emissions have been widely observed from ultrasmall thiolated gold nanoparticles (AuNPs) but remain a mystery in fundamental understanding of photoluminescence mechanisms of noble metals on the nanoscale. Herein, we report a correlation between emission wavelengths and local binding geometries of a thiolate ligand (glutathione) on AuNPs with identical size (~2.5 nm) but two distinct emission wavelengths. Using circular dichroism, X-ray absorption and fluorescence spectroscopies, we found that high Au-S coordination number (CN)/high surface coverage resulted in strong Au(I)-ligand charge transfer, chiral conformation and 600 nm emission while low Au-S CN/low surface coverage led to weak charge transfer, achiral conformation and 810 nm emission. By fine tuning of surface coverage, these two size-independent emissions can be integrated into one single 2.5 nm AuNP, where a ratiometric pH response was observed due to strong energy transfer between two emission centers, opening up a new path to design ultrasmall ratiomteric pH nanoindicators.

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.

PEGylierung und Zwitterionisierung haben individuelle Auswirkungen auf die pharmakokinetischen Eigenschaften von lumineszierenden Goldnanopartikeln (AuNPs) und ihre Anreicherung in Tumoren; beide Strategien begünstigen aber eine effektive renale Clearance. Hoch effiziente und spezifische Anreicherung in Tumoren wurde für PEGylierte AuNPs beobachtet, während sich zwitterionische AuNPS zur schnellen Tumordetektion eignen. HD=hydrodynamischer Durchmesser, GS=Glutathion.