Cascade targeting strategy for antitumor transition metal complexes

<p indent="0mm">The clinical efficacy of platinum drugs, such as cisplatin, has gradually attracted public attention to the anti-tumor properties of metal complexes. However, the lack of targeted delivery and development of multi-drug resistance have impeded the progress in metal-based therapeutics. The current research focus is on obtaining novel antitumor metal complexes that demonstrate high efficacy and low toxicity. One crucial aspect being explored is the facile modification characteristic inherent to transition metal structures. By strategically introducing diverse organic ligands, it becomes possible to modulate sub-organelle localization and biomolecular targets of these metal complexes, thereby activating distinct anti-tumor mechanisms compared to platinum drugs. This review aims to summarize recent advancements in cascade targeting strategies for achieving sub-organelle enrichment and biomacromolecule targeting with metal complexes while elucidating their respective anti-tumor mechanisms. It is anticipated that this paper will provide a new research foundation and inspiration for future design endeavors focused on targeted metal-based therapeutics.