Photoactivated Multivariate Metal–Organic Frameworks for On-Demand Drug Release: The Role of Host–Guest Interactions

The development of
smart drug delivery vehicles capable
of controlled
release upon application of an external stimulus is of paramount interest
for the next generation of personalized medicine. Herein, we report
a series of six multivariate (MTV) MOFs capable of visible light-activated
drug delivery. The drug loading capacity and release rates were systematically
tuned through variation of the linker ratio between 4,4′-azobenzene
dicarboxylic acid (H2ABDA) and 4,4′-(diazene-1,2-diyl)bis(3,5-difluorobenzoic
acid) (H2ABDA(3,5-F)). The drug loading capacity, dictated
by host–guest interactions, was thoroughly explored via a combined
experimental and computational approach using two model drug or drug-like
molecules, 5-fluorouracil (5-FU) and Nile Red. Notably, the loading
capacity for 5-FU follows a “Goldilocks” profile with
a maximum loading at 33% H2ABDA(3,5-F) content. Computational
results confirm the existence of a cooperative ligand environment
that promotes strong, preferential binding at the tetrahedral/octahedral
pore window formed between two H2ABDA and one H2ABDA(3,5-F). Thus, the MTV approach enhanced capacity over the native
100% H2ABDA(3,5-F) and 0% H2ABDA(3,5-F) MOFs.
In addition to increased loading, the rate of cargo release upon green
light excitation also increased as the percentage of H2ABDA(3,5-F) in the MOF was raised, reaching a maximum release rate
of 0.9 ± 0.1% of total cargo per minute for the MOF containing
100% H2ABDA(3,5-F) MOF. The results highlight the promise
of MTV MOF design for optimizing drug delivery vehicles with relevant
payloads and patient-dictated dosing.