A soccer-ball-shaped three-dimensional DNA origami framework was assembled to serve as an exoskeleton and to direct liposome growth inside. With up to 90 available inner modification sites, cholesterol moieties were introduced as nucleation seeds, and the vesicle templating efficiency was systematically investigated with precisely regulated seed numbers and arrangements. We confirmed that a nonsaturated optimum number (n = 30) of nucleation seeds with relatively even spatial distribution was essential for achieving well-templated and highly uniform liposomes. The seed arrangement principles and effects and the liposome formation mechanisms are thoroughly discussed. The revealed key factors in the design and optimization of 3D DNA nanoframes for functional liposome production could benefit the fields of nanotechnology and molecular medicine.
Keywords: DNA origami framework; molecular medicine; nucleation seeds; spatial distribution; templated liposome.