Title : Fundamental role and essential biomedical applications of chelated metal complex combinations in cancer therapy
Abstract:
Cancer remains one of the leading causes of mortality worldwide, necessitating the continuous development of innovative therapeutic strategies. Chelated metal complexes have emerged as crucial players in the realm of cancer therapy due to their ability to modulate biological targets effectively. The stability of these metal-complex combinations is primarily influenced by the type of chelator, the metal involved, and the coordination geometry. Metals such as Platinum Pt (II), Gadolinium Gd (II) , Palladium Pd (II) and Gold can undergo chelation, leading to various biomedical applications, particularly in oncology. Chelated metal complexes can act through multiple main mechanisms: DNA Interaction: Many metal complexes demonstrate a strong affinity for DNA, leading to the formation of covalent bonds with nucleobases. Platinum-based agents, like cisplatin, disrupt DNA replication and transcription, prompting apoptosis in cancer cells. Reactive Oxygen Species (ROS) Production: Certain chelated metals can induce oxidative stress by generating ROS, destroying cellular components such as damaged molecules of lipids, proteins, and also damaged DNA. This mechanism is exploited in therapies to induce cell death, particularly in tumor cells. Targeted Drug Delivery: Chelated metal complexes can be engineered for targeted delivery. By attaching ligands or antibodies, these complexes can preferentially bind to cancer cell receptors, ensuring localized treatment and minimizing systemic toxicity. Some Platinum Pt 0II) derived metal complexes are fundamental for their anticancer action: Cisplatin (Cis Diammine-Dichloro-Platinum(II)) is an essential Platinum-based chemotherapeutic agent which forms strong covalent bonds with DNA, causing cross-linking and ultimately inducing apoptosis. That chelated Platinum Pt (II) complex is widely used to treat various cancers, including testicular, ovarian, bladder, and lung cancers. Carboplatin (1,1-Cyclobutanedicarboxylic acid), represents a second-generation platinum-based Pt (II) drug, which interacts with DNA but has a more favorable side effect profile and is less susceptible to drug resistance. It is Often used in ovarian cancer treatment and in combination chemotherapy for lung cancer. Oxaliplatin, Platinum (2+) ethanedioate - 1,2-cyclohexanediamine (1:1:1), is another platinum-based agent is frequently used in combinatory therapies. Induces DNA damage through the formation of cross-links, particularly in cancer cells resistant to cisplatin. It is primarily used in effective treatment of colorectal cancer. Ongoing research aims to refine these complexes to enhance selectivity, reduce side effects, and overcome resistance mechanisms. Furthermore, the development of multifunctional chelated metal complexes that combine therapeutic and imaging capabilities represents a significant advancement in personalized medicine. These innovations promise to improve treatment efficacy, provide real-time monitoring, and tailor therapies to individual patient profiles.
