Host–Guest Interactions Govern Drug Stability and Controlled Therapeutic Release: Based on Metal–Organic Frameworks as Smart Platforms

Abstract

Due to their exceptional porosity, structural versatility, and modular coordination chemistry, metal–organic frameworks (MOFs) have emerged as versatile platforms for targeted drug delivery. These structures enable fine‐tuning of pore size, surface activity, and framework stability for the encapsulation of a broad range of therapeutics, including small‐molecule drugs and biomacromolecules such as nucleic acids, proteins, and peptides. In this review, the main principles governing MOF formation, drug encapsulation strategies, and molecular interactions that control host–guest behavior are described in detail. This review focuses on stimuli‐responsive and novel MOF systems that can deliver drugs in response to pH, redox reactions, enzymes, light, magnetic fields, and other biological stimuli to treat diseases. Other hybrid and composite systems, including those with polymers, lipids, hydrogels, and inorganic nanoparticles, are also discussed here. This work examined how these multifunctional systems can be enhanced in terms of their stability, targeting capabilities, and therapeutic potential. The main treatment applications, including anticancer, antimicrobial, anti‐inflammatory, cardiovascular, and gene delivery, are discussed, including synergistic interventions and combination therapies. Important factors involved in biocompatibility, toxicity, pharmacokinetics, and biodegradation are examined to assess the translational potential of MOF‐based therapeutics. Current challenges and limitations are identified, and future directions are addressed, including computationally guided and bioinspired designs, immune‐evasive coatings, theranostic MOFs, and eco‐friendly and scalable manufacturing. Overall, these results highlight the potential of MOFs for drug delivery. Their amenability to modifications and their unique tunability, multimodality, and intelligent responsiveness make them promising candidates for precision medicine and advanced therapeutic strategies.