A New Charge Reversal PCL-Block-Polyhistidine Nanoprticles for Nuclear Targeting Drug Delivery

Poly (L-histidine) (polyhis) has an endosomal membrane disruption activity due to its imidazole groups. It would be useful for cytosolic delivery of anticancer drug. However, its low aqueous solubility limits its application. We amidized its imidazole groups and thus substantially enhanced its water solubility. Its block copolymer with PCL could form nanoparticles with a size of around 130 nm. The nanoparticles are negatively charged at pH 7.4 but become positively charged at pH 5.0 due to the hydrolysis of the amides. The nanoparticles can go into nuclei within five hours for effective nuclear drug delivery. CPT and DOX loaded in the nanopartricles had higher cytotoxicity than the free drug.