Emerging ultrasmall luminescent nanoprobes for in vivo bioimaging

Photoluminescence (PL) imaging has become a fundamental tool in disease diagnosis, therapeutic evaluation, and surgical navigation applications. However, it remains a big challenge to engineer nanoprobes for high-efficiency in vivo imaging and clinical translation. Recent years have witnessed increasing research efforts devoted into engineering sub-10 nm ultrasmall nanoprobes for in vivo PL imaging, which offer the advantages of efficient body clearance, desired clinical translation potential, and high imaging signal-to-noise ratio. In this review, we present a comprehensive summary and contrastive discussion of emerging ultrasmall luminescent nanoprobes towards in vivo PL bioimaging of diseases. We first summarize size-dependent nano-bio interactions and imaging features, illustrating the unique attributes and advantages/disadvantages of ultrasmall nanoprobes differentiating them from molecular and large-sized probes. We also discuss general design methodologies and PL properties of emerging ultrasmall luminescent nanoprobes, which are established based on quantum dots, metal nanoclusters, lanthanide-doped nanoparticles, and silicon nanoparticles. Then, recent advances of ultrasmall luminescent nanoprobes are highlighted by surveying their latest in vivo PL imaging applications. Finally, we discuss existing challenges in this exciting field and propose some strategies to improve in vivo PL bioimaging and further propel their clinical applications.