Nanoscale metal-organic frameworks: From synthesis and multifunctional design to anticancer applications

Diagnosis and treatment are typically separate procedures, and their integration into theranostics holds great promise for precision medicine. Metal-organic frameworks (MOFs), assembled from metal nodes and organic ligands, are versatile platforms for multifunctional theranostics due to their integratable components and porous structure for loading active species. However, fabricating nanoscale MOFs (NMOFs) is essential for biomedical applications, as nanosize is required to cross physiological barriers for effective delivery. This review provides a critical overview of NMOF synthesis and design strategies for anticancer applications. Synthesis methods are organized from a mechanistic perspective, including self-limiting growth, seed-growing, template-assisted, kinetic-control, and competitive coordination-induced strategies, and are compared in terms of scalability, reproducibility, and pharmaceutical suitability. We then discuss MOF-based single imaging and therapy, imaging-guided drug delivery, and drug-free cancer theranostics. The combination of MOFs with nanozymes, either as carriers or/and intrinsic nanozymes, is also addressed. Finally, the toxicity profile, challenges, and future prospects for translational applications of NMOFs are outlined. In conclusion, the clinical translation of MOF-based theranostics remains in its early stages, and substantially greater efforts are required before high-performance NMOFs can reach clinical application.