2.B.55. The Phospholipid-mimicking Cell-penetrating Polymer (PCP) Family
Understanding the interactions of eukaryotic cellular membranes with nanomaterials is required to construct efficient and safe nanomedicines and for molecular bioengineering. Intracellular uptake of nanocarriers by active endocytosis limits the intracellular distribution to the endosomal compartment, impairing the intended biological actions of the cargo molecules. Nonendocytic intracellular migration is another route for nanomaterials with cationic or amphiphilic properties to evade the barrier function of plasma membranes. Direct transport of nanomaterials into cells is efficient, but this may cause cytotoxic or biocidal effects by disrupting the biological membrane barrier. Goda et al. 2020 discovered that nonendocytic internalization of synthetic amphipathic polymer-based nanoaggregates that mimic the structures of natural phospholipids can occur without inducing cytotoxicity. Analyses using a proton leakage assays indicated that the polymer enters cells by amphiphilicity-induced membrane fusion rather than by transmembrane pore formation. These noncytotoxic cell-penetrating polymers may find applications in drug delivery systems, gene transfection, cell therapies, and biomolecular engineering.