2.B.47.  The Cell Membrane Permeant Polymer (CMPP) Family  

Unlike the majority of nanomaterials designed for cellular uptake via endocytic pathways, some of the functional nanoparticles and nanospheres directly enter the cytoplasm without overt biomembrane injuries.  A water-soluble nanoaggregate composed of an amphiphilic random copolymer of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate (BMA), poly(MPC-random-BMA) (PMB), passes live cell membranes in an endocytosis-free manner. Goda et al. 2019 elaborated a pH perturbation assay that is sensitive to pore formation in cell membranes. Sensitivity originates from the detection of the smallest indicator H⁺ (H3O⁺) passed through the molecularly sized transmembrane pores upon challenge by exogenous reagents. Water-soluble PMB at the 30 mol % MPC unit (i.e., PMB30W) penetrated into the cytosol of model mammalian cells without proton leaks, in contrast to conventional cell-penetrating peptides, TAT and R8 as well as the surfactant, Triton X-100. Exposure to PMB30W allowed export of cytoplasmic lactate dehydrogenase out of the cells, indicating an alteration of cell membrane polarity by partitioning of amphiphilic PMB30W into the lipid bilayers. Nevertheless, the biomembrane alterations by PMB30W did not exhibit cytotoxicity (Goda et al. 2019).