Gold-Tagged Polymeric Nanoparticles with Spatially Controlled Composition for Enhanced Detectability in Biological Environments

Organic nanoparticles offer the advantage of high biocompatibility for biomedical applications but suffer frequently from poor visibility in biological environments. While fluorescent-labeling is convenient and allows for fast and extensive histological analysis, fluorescence imaging and quantitative analysis are limited by low resolution and significantly hindered by tissue autofluorescence. Labeling of polymeric nanoparticles with an additional gold tag would allow for high resolution imaging via transmission electron microscopy (TEM) and for quantification of particles by inductively coupled plasma optical emission spectrometry (ICP-OES). However, spatially uncontrolled gold-tagging can cause significant fluorescence quenching. To overcome this restraint, 2.2 nm gold nanoparticles were introduced at the interface between the hydrophobic fluorophore-loaded core and the hydrophilic shell of polymeric nanoparticles. Due to the small size of gold labels and the spatially controlled stratified composition of hybrid nanoparticles, fluorescence quenching by gold tags was minimized to 15.1%, allowing for concomitant detection of both labels via optical microscopy after enhancement of the gold tags. Multilayered hybrid nanoparticles exhibited outstanding detectability in TEM, even without additional sample staining. Furthermore, they were capable of producing remarkable image contrast inside cells after gold or silver enhancement. The interfacial gold layer increased the hydrodynamic particle size only marginally from 71.8 to 89.5 nm and had no negative impact on biocompatibility in vitro. The gold content (0.75% m/m) is sufficiently high for future quantification in tissues after systemic administration. With their clean-cut structure and superior detectability, multilayered hybrid nanoparticles constitute an outstanding blueprint and a precious tool for the development of nanomedicines