Duplex metal co-doped carbon quantum dots-based drug delivery system with intelligent adjustable size as adjuvant for synergistic cancer therapy

Carbon quantum dots (CQDs) are extensively applied for bioimaging due to their unique photoluminescence properties, while less attention has been paid to their inherent bio-functions as targeted drug delivery vehicles. To address this limitation, a novel CQDs-based drug delivery system (Arg-Ag@Cu) was constructed using L-arginine as precursor with duplex metal co-doping (Ag&Cu) for further DOX-loading/releasing and synergistic tumor theranostics. Specifically, the functional residues retention ability of CQDs guaranteed the reactive nitrogen species (RNS) replenishment, Ag-doping enhanced the photoluminescence intensity, and Cu2+-functionalizing could act as the anchor for further interparticle self-assembly, resulting in intelligent adjustable CQDs size for increasing the drug-loading capacity. After reaching targeted sites, CQDs could act as NO/ONOO- donors for gas-involving therapy, and Cu2+ could not only generate ROS through chemodynamic therapy (CDT), but also modulate the band structure of as-prepared CQDs for laser-induced photodynamic therapy (PDT) to further replenishing ROS. Simultaneously, with Cu2+ depletion, the structure of Arg-Ag@Cu was disrupted, which guaranteed in situ DOX-releasing. As such, these orchestrated procedures fully exerted the intrinsic bio-functions of CQDs then act as adjuvants in drug delivery systems, thus representing synergistic effects in suppressing tumor progression and migration with minimal side effects, and provides a paradigm of potent CQDs-based nanotheranostics. (C) 2021 Elsevier Ltd. All rights reserved.