Nanoparticle shape plays an important role in targeted drug delivery. Investigations of how differences in morphology affect nanoparticle-cell interactions at the single-particle level—especially internalization and cellular trafficking—are critical yet limited. Using dual-mode optical imaging tools, we compared the single-particle dynamics of aptamer-conjugated gold nanostars and gold nanospheres on cancer cell membranes. Despite the protein corona surrounding the nanoconstructs, we found that targeting nanostars showed significantly faster velocities and transited larger areas on cell membranes compared to targeting nanospheres with similar physiochemical properties. We attribute these differences in dynamics to the positive and negative curvatures on nanostars that enable both molecular and structural valency for binding overexpressed cell-membrane receptors.
