Inter-Nanoparticle FRET for Biosensing: Photophysics Versus Size

Förster resonance energy transfer (FRET) enables the quantification of nanoscale distances and biomolecular interactions. Luminescent nanoparticles (NPs) are frequently combined with fluorescent dyes or proteins in FRET. However, their use in inter-NP FRET with luminescent NPs as both donor and acceptor remains less common due to the inherent size constraints that can limit FRET efficiencies. This review critically examines the early advances and current state-of-the-art of inter-NP FRET with a focus on the most commonly used NPs, namely quantum dots (QDs), upconversion nanoparticles (UCNPs), and fluorescent organic nanoparticles (FONs). We show how NP sizes, surface shells, and coatings increase FRET-distances; propose how these drawbacks can be overcome or outcompeted by the unique photophysical properties of the NPs; and discuss representative examples of inter-NP FRET for biosensing. High luminescence brightness, outstanding photostability, near-infrared excitation and emission, spectral and temporal multiplexing, and large surfaces for multifunctional bioconjugation are only some of the features that make luminescent NPs very attractive for biosensing, and FRET efficiencies up to 90% have demonstrated their potential for successful translation into bioanalytical applications.