Background: Development of controlled drug delivery systems can improve the pharmacokinetic
characteristics of drug molecules in the human body, thereby significantly improving the
utilization rate of drugs and reducing toxicity and side effects caused by their high concentrations,
which can occur when delivery is not controlled. Metal organic frameworks are a new class of very
promising crystalline microporous materials, especially when the size is reduced to the nanometer
range. Metal-organic frameworks exhibit large specific surface areas, tunable compositions, and
easy functionalization. In recent years, an increasing number of studies have reported the remarkable
advances in multifunctional nanoscale metal-organic frameworks in drug delivery.
Objective: To review the latest research involving advances in stimuli-responsive nanoscale metal
organic frameworks as drug delivery systems in controlled-release drugs.
Discussion: We first introduce the two main strategies associated with nanoscale metal organic
frameworks used in drug loading: direct assembly and post-encapsulation. We next focus on the latest
discoveries of nanoscale metal-organic framework-based stimulus response systems for drug delivery,
including pH, magnetics, light, ion, temperature, and other stimuli, as well as multiple stimulus-
responsive drug delivery systems. Finally, we discuss the challenges and future developmental
directions of nanoscale metal-organic framework-based controlled drug release.