Chain-Length- and Saturation-Tuned Mechanics of Fluid Nanovesicles Direct Tumor Delivery

Small unilamellar vesicles (SUVs), ubiquitous in organisms, play key and active roles in various biological processes. Although the physical properties of the constituent lipid molecules, i.e., the acyl chain length and saturation, are known to affect the mechanical properties of SUVs and consequently regulate their biological behaviors and functions, the underlying mechanism remains elusive. Here, we combined theoretical modeling and experimental investigation to probe the mechanical behaviors of SUVs with different lipid compositions. The membrane bending rigidity of SUVs increased with increasing chain length and saturation, resulting in differences in the vesicle rigidity and deformable capacity. Furthermore, we tested the tumor delivery capacity of liposomes with low, intermediate, and high rigidity as typical models for SUVs. Interestingly, liposomes with intermediate rigidity exhibited better tumor extracellular matrix diffusion and multicellular spheroid (MCS) penetration and retention than their ...