Engineering Persistent Luminescence Nanoparticles for Biological Applications: From Biosensing/Bioimaging to Theranostics

CONSPECTUS: Persistent luminescence nanoparticles (PLNPs) are unique optical materials emitting long-lasting luminescence after ceasing excitation. Such a unique optical feature allows luminescence detection without constant external illumination to avoid the interferences of autofluorescence and scattering light from biological fluids and tissues. Besides, near-infrared (NIR) PLNPs have advantages of deep penetration and the reactivation of the persistent luminescence (PL) by red or NIR light. These features make the application of NIR-emitting PLNPs in long-term bioimaging no longer limited by the lifetime of PL. To take full advantage of PLNPs for biological applications, the versatile strategies for bridging PLNPs and biological system become increasingly significant for the design of PLNPs-based nanoprobes. In this Account, we summarize our systematic achievements in the biological applications of PLNPs from biosensing/bioimaging to theranostics with emphasizing the engineering strategies for fabricating specific PLNPs-based nanoprobes. We take surface engineering and manipulating energy transfer as the major principles to design various PLNPs-based nanoprobes based on the interactions between nanoprobes and targets. We have developed target-induced formation or interruption of fluorescence resonance energy transfer systems for autofluorescence-free biosensing and imaging of cancer biomarkers. We have decorated single or dual targeting ligands on PLNPs for tumor-targeted imaging, and integrated other modal imaging agents into PLNPs for multimodal imaging. We have also employed specific functionalization for various biomedical applications including chemotherapy, photodynamic therapy, photothermal therapy, stem cells tracking and PL imaging-guided gene therapy. Besides, we have modified PLNPs with multiple functional units to achieve challenging metastatic tumor theranostics. The proposed design principle and comprehensive strategies show great potential in guiding the design of PLNPs nanoprobes and promoting further development of PLNPs in the fields of biological science and medicine. We conclude this Account by outlining the future directions to further promote the practical application of PLNPs. The novel protocols for the synthesis of small-size, monodisperse, and water-soluble PLNPs with high NIR PL intensity and superlong afterglow are the vibrant directions for the biomedical applications of PLNPs. In-depth theories and evidence on luminescence mechanism of PLNPs are highly desired for further improvement of their luminescence performance. Furthermore, other irradiations without tissue penetrating depth limit, such as X-ray, are encouraged for use in energy storage and re-excitation of PLNPs, enabling imaging in deep tissue in vivo and integrating other X-ray sensitized theranostic techniques such as computed tomography imaging and radiotherapy. Last but not least, PLNPs-based nanoprobes and the brand new hybrids of PLNPs with other nanomaterials show a bright prospect for accurate diagnosis and efficient treatment of diseases besides tumors.