Next-generation antibody-drug conjugated nanoparticles in metastatic breast cancer: Mechanism, clinical advances, and translational opportunities

Metastatic breast cancer (MBC) widely spreads to other organs of the body, even with the advancement in detection, screening, and treatment. To address the current challenges of MBC, antibody-drug conjugates (ADCs) are a recent technique that combines existing cancer treatments with monoclonal antibodies to deliver cytotoxic agents directly to cancer cells. The advantages of this strategy are that it directly targets specific surface-active receptors, helping to minimize damage to healthy tissue and enhancing treatment efficiency. ADCs were conceptualized to embody the “magic bullet” vision for anticancer treatment. To improve the targeted drug delivery, the therapeutic agent is encapsulated with nanoparticles and coupled with antibodies to form antibody drug conjugate nanoparticles (ACNPs), which prevent the molecular structure of the drug, enable controlled release, and minimize toxicity. Novel development approaches and combination therapy are being researched to address the resistance to ADCs. Recent investigations and clinical trials have identified numerous signalling pathways and cell surface proteins that are crucial for cancer cell proliferation, including HER-2 and TROP-2. Unlike earlier reviews centered on conventional ADCs or nanocarriers, this article uniquely details how ACNPs can overcome the limitations of traditional ADCs, such as payload heterogeneity, limited tumour penetration, and off-target toxicity, by harnessing precision nanotechnology while also covering ADC-related patents previously undocumented in peer-reviewed literature prior to 2025.