PEGylation of nanoparticles improves their cytoplasmic transport

Junghae Suh¹, Kok-Leong Choy¹, Samuel K Lai², Jung Soo Suk¹, Benjamin C Tang², Sudhir Prabhu², Justin Hanes^1,2,3

¹Department of Biomedical Engineering; ²Department of Chemical and Biomolecular Engineering; ³The Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, USA

Abstract: The efficacy of nucleus-targeted drug or gene-carrying nanoparticles may be limited by slow transport through the molecularly crowded cytoplasm following endosome escape. Cytoskeletal elements and cellular organelles may pose steric and/or adhesive obstacles to the efficient intracellular transport of nanoparticles. To potentially reduce adhesive interactions of colloids with intracellular components, the surface of model nanoparticles was coated with polyethylene glycol (PEG). Subsequently, multiple-particle tracking (MPT) was used to quantify the cytoplasmic transport rates of particles microinjected into the cytoplasm of live cells. PEGylation increased average nanoparticle diffusivities by 100% compared to unPEGylated particles (time scale of 10 s) in live cells. Faster particle transport correlated with a marked decrease in the number of particles that underwent hindered transport, from 79.2% (unmodified) to 48.8% (PEGylated). This result adds to an impressive list of positive benefits associated with PEGylation of drug and gene delivery vectors.

Keywords: PEG, polystyrene, particle tracking, cytoplasm, microinjection