The Impact of Aspect Ratio on the Biodistribution and Tumor Homing of Rigid Soft‐Matter Nanorods

The size and shape of nanocarriers can affect their fate in vivo, but little is known about the effect of nanocarrier aspect ratio on biodistribution in the setting of cancer imaging and drug delivery. The production of nanoscale anisotropic materials is a technical challenge. A unique biotemplating approach based on of rod‐shaped nucleoprotein nanoparticles with predetermined aspect ratios (AR 3.5, 7, and 16.5) is used. These rigid, soft‐matter nanoassemblies are derived from tobacco mosaic virus (TMV) components. The role of nanoparticle aspect ratio is investigated, while keeping the surface chemistries constant, using either PEGylated stealth nanoparticles or receptor‐targeted RGD‐displaying formulations. Aspect ratio has a profound impact on the behavior of the nanoparticles in vivo and in vitro. PEGylated nanorods with the lowest aspect ratio (AR 3.5) achieve the most efficient passive tumor‐homing behavior because they can diffuse most easily, whereas RGD‐labeled particles with a medium aspect ratio (AR 7) are more efficient at tumor targeting because this requires a balance between infusibility and ligand–receptor interactions. The in vivo behavior of nanoparticles can therefore be tailored to control biodistribution, longevity, and tumor penetration by modulating a single parameter: the aspect ratio of the nanocarrier.