Strategies for Enhancing Selectivity in Anticancer Metal Complexes

Anticancer metal complexes have always been a key aspect of chemotherapy. Platinum complexes such as cisplatin are commonly used. However, their lack of selectivity often leads to severe side effects. This review examines strategies that have been used to enhance the selectivity of metal complexes toward cancer cells and therefore, minimize toxicity toward healthy cells. These strategies have been categorized into passive targeting, active targeting, stimulus-responsive, structural modifications, subcellular targeting, delivery systems, external stimulus-controlled methods, and exploitation of tumor-specific biology. Each section discusses key scientific principles behind how the strategy works, examples, advantages, limitations, and recent advances or proposed methods for improvement. This Review aims to provide a consolidated resource for researchers aiming to design next-generation metal complexes with improved selectivity.