Hybrid Micelles of Carbon Quantum Dot–Doxorubicin Conjugates as Nanotheranostics for Tumor Therapy and Turn-On Fluorescence Imaging: Impact of Conjugated Structures and On–Off–On Mechanism

Carbon quantum dots (CDs) have attracted more and more attention in the field of biological imaging, while their applications are restricted due to their nonspecific fluorescence and small particle size. Herein, two pH-responsive carbon quantum dot–doxorubicin (DOX) conjugates were designed with maleic acid (MA, cis-butenedioic acid) and fumaric acid (FA, trans-butenedioic acid) as linker, respectively, which could self-assemble into unique hybrid micelles as tumor-specific carrier-free nanotheranostics. Owing to the acid-labile covalent modification with conjugated groups and the interaction with the surrounding DOX molecules, the fluorescence of CDs was completely quenched, while it could be recovered in the tumor intracellular microenvironment by acid-triggered cleavage of the fluorophore–drug conjugates, showing excellent turn-on fluorescence for effective cellular imaging. Especially, the trans conjugate with FA as linker possessed higher drug content, better drug release behavior and stronger inhibition of tumor cells than the cis one with MA as linker, demonstrating its promising potential as carrier-free nanotheranostics for future tumor treatment.