Red light-emitting carbon dots for reduced phototoxicity and photothermal/photodynamic-enhanced synergistic tumor therapy

Photodynamic therapy (PDT) has received extensive attention due to its non-invasive, photo-stimuli-responsive advantages. However, the poor dispersibility of most photosensitizers in water and non-negligible phototoxicity limit their further clinical application. To surmount this dilemma, red-emitting carbon dots (RCDs) with good photothermal conversion ability were synthesized, and photosensitizers Chlorin-e6 (Ce6) were linked onto RCDs to construct the nano-platform RCDs-Ce6 through amide reaction. In this system, RCDs can increase the dispersion of Ce6 to enhance PDT and absorb partitions of daylight to reduce phototoxicity. At the same time, RCDs-Ce6 can achieve simultaneous excitation of photothermal therapy (PTT) and PDT under a single laser, which can overcome the drawbacks of monotherapy while simplifying the treatment procedure. Besides, the excellent fluorescence imaging capability of RCDs-Ce6 could achieve imaging-guided tumor treatment. Spontaneously, both the cytological and 3D multicellular spheroids (3D MCS) levels demonstrated that RCDs-Ce6 had a stronger synergic therapeutic effect with a combination index (CI) of 0.278 and lower phototoxicity. Meanwhile, in vivo experiments showed that RCDs-Ce6 (PTT and PDT) had a more substantial tumor inhibition effect and fluorescence imaging ability with more tumor distribution. This study widened the way for further applications of photodynamic-enhanced therapy with reduced phototoxicity in photosensitizer delivery based on RCDs.