Abstract Persistent luminescent nanoparticles store excitation energy and emit photons long after stimulus removal, enabling background‐free signals by minimizing tissue autofluorescence and the constraints of concurrent illumination. This review synthesizes recent progress in materials‐level control of persistent luminescence and its biomedical use. This outlines mechanisms of charge trapping and release, then discusses strategies to modulate emission wavelength, intensity, and duration through defect engineering, trap‐depth distribution, core–shell architectures, lattice/strain control, and surface modification. Recharge modalities spanning optical/near‐infrared (NIR), X‐ray, radionuclide, and ultrasound‐coupled routes are compared with respect to penetration, safety, and in vivo practicality. Applications include high‐contrast imaging, ultrasensitive biosensing, long‐term cell tracking, optogenetic stimulation, and biophotochemical activation. Quantitative benchmarks are highlighted, such as afterglow half‐life, integrated photon yield, NIR‐I/II penetration, recharge efficiency, colloidal stability, biocompatibility, and clearance, and discuss manufacturing and standardization considerations. Finally, it outlines how machine learning can guide composition and defect design, predict trap landscapes, and accelerate optimization of these nanomaterials for translational studies.
Pei et al. (Mon,) studied this question.