Polymeric micelles are attractive nanocarriers for hydrophobic drug molecules such as the kinase inhibitor dactolisib. Two different poly(ethylene glycol)–poly(acrylic acid) (PEG‐b ‐PAA) block‐copolymers are synthesized, PEG(5400)‐b ‐PAA(2000) and PEG(10000)‐b ‐PAA(3700), respectively. Polymeric micelles are formed by self‐assembly once dactolisib is conjugated via the ethylenediamine platinum(II) linker (Lx) to the PAA block of the block copolymers. Dactolisib micelles with dactolisib loading content of 17% w/w show good colloidal stability and display sustained release of Lx‐dactolisib over 96 h in PBS at 37 °C, while media containing reagents that compete for platinum coordination (e.g., glutathione (GSH) or dithiothreitol (DTT)) effectuate release of the parent inhibitor dactolisib at similar release rates. Dactolisib/lissamine‐loaded micelles are internalized by human breast adenocarcinoma cells (MCF‐7) in a dose and time‐dependent manner as demonstrated by confocal microscopy. Dactolisib‐loaded micelles inhibit the PI3K/mTOR signaling pathway at low concentrations (400 × 10−9 m ) and exhibit potent cytotoxicity against MCF‐7 cells with IC50 values of 462 ± 46 and 755 ± 75 × 10−9 m for micelles with either short or longer PEG‐b ‐PAA block lengths. In conclusion, dactolisib loaded PEG‐b ‐PAA micelles are successfully prepared and hold potential for nanomedicine‐based tumor delivery of dactolisib.
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