Influence of PEGylation and Surface Charge on Biodistribution of Shortwave Infrared Emitting Nanoparticles for In Vivo Bioimaging

Nanoparticles (NPs) that are both bright in the shortwave infrared (SWIR, 1000–1700 nm) window and stable in complex biological environments are critical for advancing deep-tissue in vivo imaging. Yet, their development is hampered because strategies to confer stealth properties often compromise optical performance. Here, we apply a holistic approach, taking into account physical–chemical and photophysical properties of gold nanocluster-loaded polymeric nanoparticles (AuNCpNPs) and their interactions with biomolecules, to create a class of SWIR contrast agents combining very high brightness and stealth properties. Two PEGylation strategies are compared: post-assembly coating of preformed AuNCpNPs with amphiphilic poly(ethylene glycol) (PEG) containing polymers (Pluronic) and direct assembly of AuNCpNPs from PEG containing block copolymers. Both approaches imparted stealth properties to AuNCpNPs in vitro, as assessed using fluorescence correlation spectroscopy. However, studying in vivo pharmacokinetics revealed a strong increase in the circulation time of NPs obtained through the simple adsorption of Pluronic. Comparison of the surface properties highlight the importance of the surface potential of the NPs over the PEG molecular weight or grafting density for the obtention of stealth properties. In vivo blood vessel imaging at the whole animal level in the SWIR region proved the high potential of the so-obtained AuNCpNPs for advanced bioimaging applications.