Long-circulating three-helix micelles (3HM) comprising of peptide-polymer amphiphilic subunits have managed to achieve high accumulation & penetration in several solid tumors, such as breast, colon, pancreatic, and glioblastoma murine models. 3HM has a plasma clearance half-life of 27 hours in mice, and much lower accumulation in spleen and the gastrointestinal tracts than liposomes. However, the underlying 3HM transport mechanism has yet to be fully understood. Considering that no active targeting moiety was incorporated into particle design, and high intratumoral pressure limits convective transport, it follows that passive diffusion is the likely factor dominating 3HM accumulation in tumors. Solving Fick's diffusive flux equation while taking plasma elimination into account yields an equation that can predict tumor accumulation based on tumor vessel permeability. 3HM’s high diffusivity owing to its small size and deformability gives it advantage over liposomes in penetrating through tumor tissue, escaping size-exclusion effect of the tumor extracellular matrix, intercellular spacing distances, and tumor vessel fenestrations.

Investigating sub-20 nm nanocarrier transport and accumulation in tumors

2019 Fall National Meeting

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