Abstract 4201: Simulating trans-endothelial nanoparticle transport via macropinocytosis

Abstract Macropinocytosis is a key mechanism in transendothelial nanoparticle transport into solid tumours. It uses cell membrane ruffles to capture circulating nanoparticles. Endothelial cell ruffles cannot be independently and systematically varied in vivo, preventing parameter-specific analysis. We developed an in silico model that examines nanoparticle capture by macropinocytosis. We discover that nanoparticle capture rates rise steeply until saturating with ruffle number as well as ruffle turnover time. From our data we derive an equation describing the nanoparticle capture by macropinocytosis. This relationship reveals how ruffle dynamics govern nanoparticle capture efficiency. Citation Format: Marvin Skiba, Hae-gyung T. Han, Warren Chan. Simulating trans-endothelial nanoparticle transport via macropinocytosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4201.