Anticancer agents based on metal organic cages

Cancer is the second leading cause of death worldwide, even though various anticancer strategies have been developed. The rapid development of nanotechnologies has enhanced the performance and efficacy of conventional anticancer strategies. However, the poor controllability of most nanoagents in terms of characteristics such as size, composition, and surface chemistry presents a formidable challenge in their clinical transformation due to their ambiguous structures. As an emerging type of porous nanoobject with precise and tailorable nanostructures at the atomic level, metal organic cages (MOCs) constructed by coordination between metal clusters or ions and organic ligands have exhibited fascinating properties and functions for diverse applications. With their diversity, regulatability, porosity, modifiability, biocompatibility and stability, MOCs can serve as nanoagents in precision medicine for cancer therapy. The precise and tunable structures (components, topologies, cavities, sizes and surface features) of MOCs can not only satisfy the diverse requirements of different anticancer strategies but also promote intensive structure–property studies to guide structural design and optimize curative effects. The ultrasmall size (<20 nm generally) of MOCs can enhance their enrichment in cancer tissue through the enhanced permeability and retention (EPR) effect. Therefore, a variety of MOC-based anticancer nanoagents for different anticancer strategies have been developed and have demonstrated outstanding anticancer performances. In this review, we focus on representative anticancer applications of MOC-based nanoagents. We catalog the varied roles of MOCs in different anticancer strategies, especially for chemotherapy and photodynamic therapy. We also describe the impressive progress in multifunctional MOCs for combined therapy and theranostics. Furthermore, the prospects and challenges of employing MOCs in cancer therapy are explored and discussed.