Mitochondria-targeted metal–organic frameworks for cancer treatment

Much of the progress in subcellular targeted therapy of cancer over the past years has been driven by attacking disease cell's mitochondria. A paradigm, central to cancer biology is that mitochondrial dysfunction controls a series of the point-of-no-return metabolic changes including variation of redox status, production of reactive oxygen species, safeguarding of calcium levels, initiation of programmed cell death and the formation of mitochondria permeability transition pores. Mitochondria are also related to tumor invasion, proliferation, tumorigenesis, and metastasis and are therefore, considered as one of the most central therapeutic targets in cancer. Very recently, it has been shown that supramolecular metal–organic frameworks (MOFs) could be targeted to the tumor's mitochondria selectively using the triphenylphosphonium (TPP⁺) conjugation approach or exploiting the intrinsic cationic nature of the MOFs. Mitochondria-targeted MOFs (mitoMOFs) can significantly disrupt the metabolic processes in cancer cells either by releasing ‘classic’ chemotherapeutic drugs or by facilitating photodynamic inactivation, microwave thermal therapy and other pathways. This review discusses the design and development of novel MOF-based platforms for applications in mitochondria-targeted therapeutics and provides key insights into their mechanistic roles in achieving optimal therapeutic outcomes with minimal side-effects. Overall, mitoMOFs have a great potential to propel the field of targeted therapy and could likely change the conventional pharmacological interventions scientifically and clinically.