NUCLEOLIN and breast cancer: Even so, several biological constraints inherent to breast cancer may limit the consistency of aptamer-mediated targeting: HER2, CD44, and nucleolin exhibit heterogeneous expression across molecular subtypes and can undergo dynamic changes during disease progression or under therapeutic pressure [[180], [181], [182]], while the dense extracellular matrix, stromal remodeling, and immunosuppressive tumor microenvironment characteristic of certain subtypes can impede nanoparticle penetration and attenuate therapeutic efficacy [183,184].