Electronic descriptors and periodic trends in graphene/LDH-based nanocarriers for breast cancer drug delivery

Abstract

Nanomaterials have emerged as promising candidates for drug delivery in cancer therapy because of their ability to reduce off-target side effects. However, the rational design of novel, high-efficiency drug delivery systems (DDSs) that synergistically improve therapeutic performance and bioefficacy remains a major challenge in medicinal nanotechnology. In this work, a systematic first-principles investigation of three architecturally distinct graphene-based nanocarrier families, namely layered double hydroxide/graphene heterobilayers (LDH@G), single transition-metal-doped graphene (M@G), and their hybrid composites (LDH@G-M), was performed to establish structure–activity relationships for breast cancer drug delivery. Specifically, M3N-type layered double hydroxides (M3N-LDHs, where M and N denote distinct transition metal atoms) were identified as key structural regulatory components, while metal-graphene interfacial interaction was confirmed as a critical indicator for nanocarrier optimization. Screening 29 transition-metal dopants across six clinically relevant breast cancer drugs revealed a universal periodic first-increase-then-decrease trend in adsorption energy within each transition-metal period, which can be rationalized within d-band center theory. For gemcitabine specifically, the Bader charge and d-orbital population on the metal dopant act as effective linear descriptors of adsorption energy, providing a practical electronic-structure-based screening route. Together, these results offer valuable theoretical and practical guidance for developing next-generation nanocarriers for targeted breast cancer drug delivery.