Interaction Pathways between Plasma Membrane and Block Copolymer Micelles.

In this work, the interactions between block copolymer micelles (BCMs) and plasma membranes were investigated by performing coarse-grained molecular dynamics (CGMD) simulations. Different binding strengths between the BCMs and the membranes were tested, and four interaction pathways were discovered: attachment, semiendocytosis, endocytosis, and fusion. Endocytosis was the most efficient way for the BCMs to be taken up, and fusion could lead to cytotoxicity. Unlike rigid particles, deformation of the BCMs strongly affected the interaction pathways. We examined the effects of changing the aggregation number of the BCMs (Nagg), the chain length of the polymer (Nb), and the chain stiffness of the hydrophobic block (ka), and we learned that smaller Nagg and lower Nb could lead to weaker cellular uptake capacities, whereas larger Nagg and higher Nb gave rise to higher cytotoxicities. Moreover, a weaker chain stiffness of the hydrophobic block could be more favorable for obtaining BCMs with higher internalization efficacies and lower cytotoxicities. The results of these simulations could aid in the design of BCMs with desirable cellular internalization capacities and lower cytotoxicities. Such BCMs could be useful in drug-delivery systems.