Enzyme-responsive 2-dimensional nanomaterials for targeted breast cancer treatment

Breast cancer remains one of the most prevalent causes of cancer deaths globally. This is because systemic toxicity, multidrug resistance and poor tumour selectivity typically make treatment less effective. Traditional drug delivery methods depend heavily on passive targeting and diffusion-controlled release. Enzyme-responsive drug delivery systems have recently been developed as a biologically precise approach that takes clinical advantage of the specialised enzymatic environment of breast tumours, such as the overproduction of matrix metalloproteinases, cathepsins and hyaluronidase. Among advanced nanocarriers, two-dimensional (2D) nanomaterials have attracted significant attention because of their high surface-to-volume ratio, ultrathin planar structure, tuneable surface chemistry, and exceptional drug-loading capacity. Graphene derivatives, black phosphorus, layered double hydroxides, transition metal dichalcogenides, and MXenes are all examples of materials that can be used to make enzyme-cleavable linkers. This paper critically discusses the enzymatic characteristics of the breast tumour microenvironment, design principles of enzyme-responsive linkers, classifications and physicochemical properties of 2D nanomaterials and their functionalization strategies. Furthermore, toxicity considerations, preclinical advancements, translational barriers, and future perspectives are analysed. Collectively, enzyme-responsive 2D nanomaterials represent a promising next-generation approach for precision breast cancer therapy, offering improved targeting efficiency, controlled drug activation, and potential theranostic integration.