Ultra-bright and stimuli-responsive fluorescent nanoparticles for bioimaging

Fluorescent nanoparticles (NPs) are unique contrast agents for bioimaging. Examples of molecular-based fluorescent NPs with brightness similar or superior to semiconductor quantum dots have been reported. These ultra-bright NPs consist of a silica or polymeric matrix that incorporate the emitting dyes as individual moieties or aggregates and promise to be more biocompatible than semiconductor quantum dots. Ultra-bright materials result from heavy doping of the structural matrix, a condition that entails a close mutual proximity of the doping dyes. Ground state and excited state interactions between the molecular emitters yield aggregation-caused quenching (ACQ) and proximity-caused quenching (PCQ). In combination with Föster resonance energy transfer (FRET) ACQ and PCQ originate collective phenomena that produce amplified quenching of the nanoprobes. In this focus article, we discuss strategies to achieve ultra-bright nanoprobes avoiding ACQ and PCQ also exploiting aggregation-induced emission (AIE). Amplified quenching, on the other hand, is also proposed as a strategy to design stimuli-responsive fluorogenic probes through disaggregation-induced emission (DIE) in alternative to AIE. As an advantage, DIE consents to design stimuli-responsive materials starting from a large variety of precursors. On the contrary, AIE is characteristic of a limited number of species. Examples of stimuli-responsive fluorogenic probes based on DIE are discussed.