pH/Reduction dual-responsive comet-shaped PEGylated CQD-DOX conjugate prodrug: Synthesis and self-assembly as tumor nanotheranostics

Carbon quantum dots (CQDs) show promising potential for tumor imaging owing to their unique superior fluorescent properties. However, the small particle size limits their practical application. Here, pH/reduction dual-responsive comet-shaped PEGylated CQD-DOX conjugate prodrug, DOX-Hy-CQD-SS-PEG with DOX content of 28.5%, was designed with the hydrophobic acid-labile DOX conjugated CQDs as comet nucleus and the few hydrophilic bioreducible detachable PEG brushes as comet tails. The comet-shaped DOX-Hy-CQD-SS-PEG prodrug could self-assemble into unique micelles with mean diameter of 127 nm. The DOX-Hy-CQD-SS-PEG micelles possessed excellent pH/reduction dual-responsive drug release with low drug leakage of 9% in 150 h. Furthermore, the fluorescent CQDs was recovered after DOX release and de-PEGylation, demonstrating their potential application for real-time response of therapy.