Cyclodextrin-based metal-organic frameworks (MOFs) as delivery systems for quercetin: Effects of carrier size and protein corona formation.

Understanding how carrier size influences protein corona formation and delivery behavior is important for the rational design of γ-cyclodextrin-based metal-organic frameworks (γCDMOFs). In this study, micron-scale (microMOF) and nanoscale γCDMOFs (nanoMOF) were compared as quercetin carriers using pepsin and human serum albumin as model proteins. NanoMOF (∼350 nm) exhibited a higher specific surface area (1016.01 m2/g vs. 769.79 m2/g) and encapsulation efficiency (85.37% vs. 65.24%) than microMOF (∼2.16 μm). Protein adsorption showed size-dependent differences, with nanoMOF exhibiting greater protein adsorption and a higher proportion of tightly bound protein. For quercetin-loaded carriers, pepsin adsorption reached 1224.15 ng/cm2 on nanoMOF compared with 834.08 ng/cm2 on microMOF. The pepsin-coated nanoMOF showed ∼28% quercetin release after 2 h of gastric digestion, followed by ∼92% cumulative release after 6 h. NanoMOF-based systems also retained higher antioxidant activity. These findings demonstrate that carrier size influences protein corona characteristics and quercetin delivery behavior in γCDMOF systems.