Development of Protein-Cage-Based Delivery Nanoplatforms by Polyvalently Displaying beta-Cyclodextrins on the Surface of Ferritins Through Copper(I)-Catalyzed Azide/Alkyne Cycloaddition

Abstract

Protein cages are spherical hollow macromolecules that are attractive platforms for the construction of nanoscale cargo delivery vehicles. Human heavy-chain ferritin (HHFn) is modified genetically to control the number and position of functional groups per cage. 24 beta-CDs are conjugated precisely to the modified HHFn in specific locations through thiol-maleimide Michael-type addition followed by copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC). The resulting human ferritins displaying beta-CDs (beta-CD-C90 HHFn) can form inclusion complexes with FITC-AD, which can slowly release the guest molecule reversibly in a buffer solution via non-covalent beta-CD/AD interactions. beta-CD-C90 HHFn can potentially be used as delivery vehicles for insoluble drugs.