Formulation Innovations Targeting ACTB Pathways in Breast Cancer: From Cytoskeletal Dysregulation to Precision Drug Delivery

Breast cancer remains the most prevalent malignancy among women worldwide, contributing significantly to cancer-related morbidity and mortality. The actin cytoskeleton protein ACTB (β-actin) has emerged as a pivotal player in breast cancer progression, orchestrating cytoskeletal remodeling that fuels tumor invasion, metastasis, and resistance to conventional therapies through its regulation of critical pathways such as NF-κB and Wnt/β-catenin. This review aims to synthesize recent advances in formulation strategies designed to selectively target ACTB-mediated signaling in breast cancer. Key focus areas include the mechanistic role of ACTB within cytoskeletal and metastatic cascades, and the translation of molecular insights into innovative drug delivery approaches. Highlighted are nanoparticle-based formulations—such as liposome-encapsulated ACTB-siRNA, targeted polymeric nanoparticles, gold nanoconjugates, dendrimers, and exosome-mimicking carriers—that demonstrate enhanced specificity, efficacy, and tumor penetration in preclinical models. The review further discusses ongoing clinical studies and the hurdles of translating ACTB-targeted formulations into effective therapies, including challenges of tumor heterogeneity, bioavailability, and regulatory milestones. Looking forward, the integration of AI-driven formulation design, biomarker-guided personalization, and combination therapeutic strategies are underscored as essential for realizing next-generation, ACTB-targeted precision nanomedicines in breast cancer management.