Lanthanide-Doped Inorganic Nanoprobes for Luminescent Assays of Biomarkers

Conspectus Tremendous progress in nanomaterial and nanotechnology has been made in recent years, which greatly contributes to the development of inorganic nanoparticles (NPs) as luminescent probes in diverse biomedical applications. In particular, these luminescent nanoprobes are widely employed for sensitive assays of biomarkers like disease markers. Generally, the luminescent bioassay technologies mainly rely on conventional molecular probes such as lanthanide (Ln 3+ ) chelates or organic dyes, which suffer from inferior photochemical stability, low photobleaching, potential long-term toxicity, or high background noise. In contrast, Ln 3+ -doped NPs possess distinct physicochemical properties including better photostability, lower toxicity, and superior optical properties like long photoluminescent (PL) lifetime, narrow emission band, and tunable spectral range from the ultraviolet to the second near-infrared (NIR-II), which make them extremely ideal as luminescent nanoprobes. As such, enormous research enthusiasm has been invested in this fascinating field of Ln 3+ -doped luminescent nanoprobes in recent years. Accordingly, background-free luminescent bioassays with high signal-to-noise have been achieved by employing Ln 3+ -doped NPs on the basis of their downshifting luminescence (DSL) with a long PL lifetime, NIR-II luminescence with long-wavelength emissions, or upconverting luminescence (UCL) upon NIR excitation. However, there are still key challenges for Ln 3+ -doped nanoprobes owing to their low brightness and quantum yield, which restrict their biomedical applications. During the past decade, we have explored efficient approaches for the synthesis and design of highly efficient Ln 3+ -doped nanoprobes toward ultrasensitive luminescent bioassay of disease markers. In this Account, we summarize our most recent endeavors toward the development of inorganic Ln 3+ -doped NPs as sensitive nanoprobes for luminescent bioassays. First, we overview the approaches of controlled synthesis and optical manipulation to obtain highly efficient Ln 3+ -doped NPs with desirable optical properties. Second, we survey the design of Ln 3+ -doped nanoprobes with outstanding water dispersibility and excellent biocompatibility through surface functional bioconjugation of NPs. By employing these nanoprobes, we propose and exemplify several background-free luminescent bioassay strategies in an effort to suppress the interference of background noise from scattered lights and autofluorescence from biological samples. Third, we highlight the ultrasensitive bioassay of disease markers such as the time-resolved luminescent bioassay, NIR-II luminescent bioassay, and UCL bioassay. Finally, the major challenges, promising emerging trends, and future perspectives on this attractive field are discussed. Through this Account, we aim to offer a series of effective approaches to luminescent bioassay with high sensitivity and excellent specificity based on Ln 3+ -doped nanoprobes, which may broaden the roadway for clinical bioassays and accelerate the exploration of novel nanoprobes in versatile biomedical applications.