We report on a cationic liposome (CL) nanoparticle (NP) system loaded with hydrophobic paclitaxel (PTX) in which PEGylation (i.e. PEG-CL<sub>PTX</sub> NPs) unexpectedly enhances, rather than diminishes, delivery efficacy to human cells. This highly unexpected enhancement occurs even when the PEG-chains coating the NP are in the transition regime between the mushroom and brush conformations. Cryogenic TEM of PEG-CL<sub>PTX</sub> NPs shows that PEG causes proliferation of a mixture of sterically stabilized nanometer-scale vesicles and anisotropic micelles (nanodiscs). Onset of nanodiscs at sub-monolayer concentrations of the PEG-coat is unexpected and PEG-lipid in this composition regime was not thought to alter NP shape. Confocal microscopy and flow cytometry reveal significantly greater PTX cell uptake from stabilized nanodisc NPs in contrast to bare CLs which can aggregate in cell medium. These results are in contrast to PEGylated CL-DNA NPs employed in gene therapeutics, where the PEG coat suppresses cell entry.

PEGylation of paclitaxel-loaded cationic liposomes drives a shape transition from spheres to nanodiscs and enhances delivery to human cancer cells

ACS Spring Meeting 2021

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