Nanoformulation of metal complexes: Intelligent stimuli-responsive platforms for precision therapeutics

Precision medicine is a potential effective therapeutic for various human diseases. Currently, metal complex-based drugs are being successfully used in clinical applications owing to diverse properties such as multiple redox states, photo-induced ligand exchange, and preferential ligand and coordination numbers, which facilitate drug design and development. However, drawbacks such as toxicity, lack of specificity, and severe side effects have hampered their therapeutic outcome. Therefore, innovative strategies for improving the specificity and pharmacokinetics of conventional metal complex-based therapeutic agents are required. Recently, nanotechnology, which provides a unique toolbox for developing effective and safer medicine, has attracted considerable attention, mainly because of their ability to reduce side effects and enhance drug loading efficiency and pharmacokinetics. Considering the promising chemical and physical properties of diverse nanostructures, nanoformulation of metal complexes can be used to effectively address the problems associated with current metallodrug complexes, especially those based on stimuli-responsive therapeutic strategies, with excellent spatial, temporal, and dosage control. In this review, we have mainly focused on the specificity and environment-responsiveness of metallodrug nanoformulations as therapeutics, and summarized the recent strategies being used for developing metal complex-functionalized intelligent nanoplatforms, which respond to various types of stimuli, including endogenous signals (pH, redox conditions, and enzyme activities) or external triggers (light irradiation and magnetic field manipulations). In addition, we have also discussed the potential challenges associated with use of metallodrugs and their nanoformulations as effective precision therapy with improved specificity and minimal side effects.