ROS generation/scavenging modulation of carbon dots as phototherapeutic candidates and peroxidase mimetics to integrate with polydopamine nanoparticles/GOx towards cooperative cancer therapy

Abstract

In this study, the reactive oxygen species (ROS) scavenging or generation ability of the carbon dots (CDs) was regulated by incorporating with heteroatoms (Cu and Cl ions). The pristine CDs were found to be powerful anti-oxidants to scavenge ROS, with half-maximal inhibitory concentrations (IC50) of • O 2 − and • OH radicals estimated to be 6.89 and 6.12 μg/mL, respectively, whereas Cu and Cl co-doped CDs (CuCl-CDs) possessed not only ROS generation ability upon laser irradiation for photodynamic therapy (PDT), but also peroxidase-mimic activity that generates oxidative •OH from hydrogen peroxide (H 2 O 2 ) for chemodynamic therapy (CDT). Moreover, the colorimetric assay, 1 O 2 emission peak, and ESR results supported the efficient production of •O 2 − , •OH, and 1 O 2 radicals. Furthermore, CuCl-CDs with ROS-generating abilities and peroxidase-mimetic properties were successfully integrated with polydopamine (PDA) and glucose oxidase (GOx) to fabricate multifunctional GOx/CuCl-CD@PDA-PEG (GCP) nanocomposites with hydrodynamic sizes of 135.5 nm. These novel GCP nanocomposites possessed satisfactory photothermal conversion efficacies (η = 24.4%) and gave a high yield of ROS via the combination of H 2 O 2 and laser irradiation. Moreover, the presence of GOx in GCP nanocomposites enables these compounds to decrease the intracellular glucose levels for starvation therapy and the enzymatic cascade activity for enhanced ROS-mediated therapy. In vitro studies and confirmed that these GCP nanocomposites displayed good biocompatibility with concentrations from 100 to 1000 ppm, but induced 90% reduction in B16F1 cell viability at 200 ppm via the cooperative effects of CDT, phototherapeutic effect, and starvation therapy. • Carbon dots without heteroatom incorporation exhibited antioxidant characteristics. • The incorporation of Cu and Cl ions inside carbon dots enabled ROS generation capability. • CuCl-CDs was coupled with PDA and GOx to construct multifunctional nanocomposites. • Multifunctional nanocomposites serve as phototherapeutic and starvation-inducing agents for cooperative cancer therapy.