Emergent phase architectures in 2D materials for multimodal cancer therapy

Cancer therapy has advanced significantly, but conventional treatments still face limitations, including low selectivity, severe side effects, and therapy resistance. Two-dimensional (2D) materials have emerged as promising candidates for overcoming these challenges due to their tunable electronic, optical, and chemical properties. While traditional optimization strategies such as size engineering, surface functionalization, and doping have improved 2D material performance, they often fail to balance stability, safety, and multifunctionality. Phase engineering offers a more precise approach by enabling control over phase transitions, defects, interlayer interactions, and heterostructures, enhancing the therapeutic efficacy of 2D materials. This review classifies 2D materials into categories such as graphene, metal oxides, metal hydroxides, metal carbides and nitrides, and porous organic frameworks, exploring how phase engineering strategies, including phase transition regulation, defect introduction, interlayer rearrangement, and heterostructure construction, impact applications like photothermal therapy, drug delivery, and catalytic therapy. By shifting focus from single-property optimization to an integrated approach, the review provides a comprehensive understanding of how phase engineering enhances the multifunctional and synergistic therapeutic properties of 2D materials. It also addresses the knowledge gap regarding the structure–activity relationships between phase structures and cancer treatment outcomes, offering new insights for the development of advanced cancer therapies. This review offers a phase engineering perspective that explains how atomic-scale factors such as phase transitions, defect structures, interlayer coupling, and heterostructure topology control the efficacy, selectivity, safety, and clinical potential of two-dimensional materials in multimodal cancer therapy. • Defines a phase-guided paradigm linking atomic structure modulation with therapeutic function in 2D materials. • Unveils energy–biological coupling mechanisms that drive multi-modal cancer therapy at the nanoscale. • Establishes a unified concept of catalytic–optical synergy, advancing next-generation precision nanomedicine.