Intrinsically stealth fluorescent organic nanoparticles made of articulated bis-dipolar dyes for single particle tracking

Luminescent nanoparticles are becoming fundamental tools to the field of bioimaging. The optimization of their size, brightness and stability is key for applications ranging from contrast agent assisted surgery to diagnosis and therapeutics. A plethora of formulations have been documented which can be split into inorganic, organic and hybrid categories. While each class has their own advantages and limitations, controlling the interactions occurring between nanoparticles and cellular membranes is of the utmost importance. In particular, a major challenge for various applications, especially molecular imaging of membrane receptors, is to prevent non-specific interactions. Towards this goal, popular strategies based on coating nanoparticles with PEG or zwitterionic moieties have been developed to yield stealth nanoparticles. In this study, we present a series of spontaneously water-soluble and stealth organic nanoparticles. These fluorescent nanoparticles, made from original articulated bis-dipolar dyes, show vanishing interactions with living cells as bare nanoparticles. Moreover, thanks to their brightness and stability, they can be tracked as isolated single emitters in aqueous environments. These stealth nanoparticles thus hold promise for molecular imaging of specific membrane receptors, such as neuronal receptors, after bioconjugation with dedicated targeting agents.