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

Breast cancer is still one of the most prevalent causes of cancer deaths globally. This is because systemic toxicity, multidrug resistance and poor tumor selectivity typically make treatment less effective. Traditional drug delivery methods depend heavily on passive targeting and diffusion-controlled release. This leads to drugs leaking out too soon and not working as well as they could. Enzyme-responsive drug delivery systems have recently been developed as a biologically precise approach that takes clinical advantage of the specialized enzymatic environment of breast tumors, such as the overproduction of matrix metalloproteinases, cathepsins and hyaluronidase. Two-dimensional (2D) nanomaterials are one of the major advanced types of nanocarriers. They have a high surface-to-volume ratio, an ultrathin planar structure and tunable surface chemistry. They also have an 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. These properties help to provide targeted and controlled release of the drug. This paper critically discusses the enzymatic characteristics of the breast tumor 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 analyzed. 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.