Metal-based antibody, nanobody, and peptide conjugates: Potential for breast cancer therapy

Globally, breast cancer (BC) remains the leading cause of cancer death in women. BC profoundly impacts the physical and psychological well being of millions of families worldwide and significantly burdens the healthcare system and the economy. Although chemotherapy remains a key component in BC treatment, its effectiveness is often limited by severe side effects and the development of drug resistance, highlighting the urgent need for innovative therapeutic strategies. One strategy to minimize side effects involves conjugating anticancer agents with tumor-targeting molecules such as antibodies, nanobodies, or peptides to enhance their selective delivery to cancer cells. The success of platinum-based drugs such as cisplatin and carboplatin has urged the exploration of other metal-based complexes as therapeutic agents for BC. Metals, including copper, zinc, and gold, are considered promising candidates for anticancer therapy because of their well established cytotoxic properties and relatively low cost. This review examines the use of metal-based agents conjugated to tumor-targeting molecules for the treatment of BC. Additionally, we propose a novel approach to conjugate innovative thiosemicarbazone-copper complexes with a targeting moiety, aiming to overcome 2 major clinical challenges of current anticancer drugs: side effects and drug resistance. SIGNIFICANCE STATEMENT: Metal-based drugs possess potent anticancer properties through diverse mechanisms. However, current agents like cisplatin face 2 major challenges common to most anticancer therapies: toxic side effects and drug resistance. One strategy to address these issues is the conjugation of anticancer agents to specific tumor-targeting moieties, such as antibodies, nanobodies, or peptides. To further limit resistance development, drug conjugates can be designed to include a potent, multitargeted payload, such as a thiosemicarbazone-copper complex that targets lysosomes.