Afterglow luminescence imaging produces long-lasting light emission after excitation ceases, enabling autofluorescence-free imaging with ultrahigh sensitivity. Compared to conventional multicomponent systems, self-sustaining afterglow molecules (SAMs) integrate photosensitization, high-energy intermediate formation, and afterglow generation based on an individual molecule, reducing system complexity and avoiding intermolecular energy transfer, thereby improving simplicity and efficiency. However, self-sustaining afterglow systems often suffer from severe intermolecular interactions, leading to an aggregation-caused quenching (ACQ) effect and suppressed photosensitization capability, ultimately resulting in a compromised afterglow signal. To address these issues, we design self-sustaining quinoid-cyanine-based afterglow scaffolds (QCAs) by incorporating steric hindrance groups to suppress intermolecular interactions and alleviate ACQ. This chemical engineering approach enhances both 1O2 generation and fluorescence, yielding a remarkable 1566-fold increase in afterglow intensity. Theoretical studies confirm that the steric hindrance groups increase the intermolecular distance, yielding looser molecular packing and interactions. Additionally, we introduce a phenylboronic acid moiety into the optimized scaffold to cage the quinone moiety, enabling ONOO–-activatable afterglow imaging. The probe enables specific in vivo afterglow imaging of subcutaneous tumors with an ultrahigh signal-to-background ratio (SBR) of 426. Finally, by functionalizing the probe with a blood–brain barrier (BBB)-permeating angiopep-2 peptide, the probe achieves a discriminative detection of mice with Parkinson’s disease (PD) from healthy controls with an imaging contrast of 6.5, which is inaccessible with fluorescence imaging. This study presents a systematic chemical engineering strategy for designing SAMs that mitigate intermolecular quenching and enable activatable afterglow luminescence.
Zhao et al. (Wed,) studied this question.