A nanocarbon-enabled hybridization strategy to construct pharmacologically cooperative therapeutics for augmented anticancer efficacy.

ABSTRACT

The drug design principles are of great value in developing nanomedicines with favorable functionalities. Herein we propose a nanocarbon-enabled hybridization strategy to construct a pharmacologically cooperative nanodrug for improved cancer therapy in the light of pharmacophore hybridization in medicinal chemistry and the synthetic principles of nanocarbons. An antioxidant defense pharmacological inhibitor and a co-nucleation precursor are structurally hybridized into nanodrugs (SCACDs) via forming carbon quantum dots. These SCACDs elicit dual enhanced bioactivities, including superior sonocatalytic activity that arose from the appropriate band structure of the pharmacophoric carbon cores, and more than an order of magnitude higher antioxidant defense inhibitory activity than the pharmacological inhibitor via conveying the bioactive pharmacophores from the molecular level to nanoscale. In vivo, SCACDs possess a long body retention and desirable biodistribution to eliminate melanoma cells at a very low injection dose. The present study provides a viable yet effective strategy for the development of pharmacologically cooperative nanodrugs to achieve remarkably improved therapeutic efficacy.