Microenvironment-responsive phosphorescence carbon dots for infection visualization and wound regeneration.

BACKGROUND

Embedding carbon dots (CDs) within protective matrices to preserve their room-temperature phosphorescence (RTP) has enabled the development of autofluorescence-free biosensing platforms based on CDs. However, current matrices are inherently inert, which inevitably restricts the bioresponsiveness and signal transduction of CDs in biosensing. Moreover, many matrix-encapsulated RTP-CDs suffer from poorly controlled particle sizes, impairing their biomedical applications. There is an urgent need to develop stimuli-responsive and size-controllable RTP-CDs to unlock their full biomedical application potential.

RESULTS

We report a universal strategy for fabricating acid-responsive and size-tunable RTP-CDs with integrated diagnostic and therapeutic functions. Specifically, levofloxacin-derived CDs were synthesized and subsequently encapsulated within CaCO3 microparticles. The as-designed CDs@CaCO3 exhibit intense aqueous RTP with a lifetime up to 383.9 ms. The particle size and RTP color of CDs@CaCO3 can be rationally modulated. CDs@CaCO3 exhibits a rapid and sensitive response to acidic microenvironments. Furthermore, it offers a linear response over a proton concentration range of 0.1-1.0 mM and excellent selectivity. In S. aureus-infected skin wounds, the CaCO3 matrix undergoes site-specific degradation in response to the acidic microenvironment and leads to significant attenuation of the RTP signal, enabling autofluorescence-free imaging of bacterial infections. Concurrently, the released levofloxacin-derived CDs effectively eradicate bacteria in wounds and accelerate wound healing within 8 days.

SIGNIFICANCE: This study establishes a generalizable paradigm for constructing disease microenvironment-responsive RTP-CDs with tunable physicochemical and optical properties, which is expected to significantly advance the applications of CDs in the diagnosis and treatment of diverse acidic pathology-associated diseases, including bacterial infections, tumors, and atherosclerosis.