Correlation of polymeric micelle sizes and their cellular internalization in vitro and tumor targeting in vivo

In order to explore the size effect of polymeric micelles on cellular internalization and tumor targeting, chrysin modified mPEG-PCL copolymer micelles with different particle sizes were fabricated to load Nile red as fluorescence probes. Four kinds of micelles with the mean sizes of 20, 40, 80 and 120 nm and narrow size distributions were prepared. The zeta potentials of the micelles were within -2 to 0 mV. The micelles were stable at low concentration (10(-3) mg mL(-1)) for a long time of storage. The micelles were incubated with C2C12 myoblasts and 4T1 breast cancer cells to investigate their cellular uptake. It was found that the cellular internalization of the polymeric micelles was dependent on the cell line and particle size. The cellular uptake of the micelles in 4T1 cells was much better than that in C2C12 cells, and the polymeric micelles with a size of 120 nm exhibited the strongest red fluorescence. The Nile red loaded polymeric micelles were injected in mice via their tail vein to study tumor targeting in vivo. The micelles were mainly accumulated in the liver and kidney, however, different from the results in vitro, the red fluorescence intensity in the tumor administrated with polymeric micelles with a size of 40 nm was the strongest compared with the other three particles, which implied that micelles with a size of 40 nm exhibited efficient tumor targeting. This work provides guidelines for the rational design of polymeric micelles as carriers for efficient targeted drug delivery.