New insights into breast cancer therapy: application and mechanisms of novel targeted nano-formulation.

As the most common malignant tumor among women worldwide, breast cancer poses substantial challenges to the effectiveness of conventional therapies because of its molecular and pathological heterogeneity, high invasiveness, and strong metastatic potential. Novel targeted nanocarrier systems can achieve efficient drug accumulation at tumor sites and precise intracellular delivery through the synergistic integration of the enhanced permeability and retention effect and surface-engineered active targeting ligands. This review systematically summarizes targeted nanomedicines constructed from mainstream carriers, including polymeric, metallic, and biomimetic nanoparticles. In terms of combinational therapeutic mechanisms, these nanomedicines can synergize with immunotherapy by activating the cGAS-STING pathway, blocking the CD47 "don't eat me" signal, and promoting the polarization of tumor-associated macrophages from the M2 to the M1 phenotype; they can enhance photodynamic and sonodynamic therapies by delivering photosensitizers or sonosensitizers to generate reactive oxygen species and induce immunogenic cell death. Moreover, they can protect gene therapeutics from degradation by encapsulating nucleic acid cargos such as siRNA, mRNA, and CRISPR-Cas9, thereby facilitating gene silencing and overcoming drug resistance. This review further focuses on the design principles of stimulus-responsive smart drug delivery systems and discusses the future prospects of artificial intelligence-assisted optimization strategies for nanomedicine development.