Multifunctional nanoparticles self-assembled from polyethylenimine-based graft polymers as efficient anticancer drug delivery

Abstract Multiple functionalization of nanoparticles has attracted great interest in drug delivery. In this paper, polymeric amphiphiles of polyethylenimine (PEI) conjugated with methoxy poly(ethylene glycol) aldehyde (mPEG-CHO), poly(e caprolactone) aldehyde (PCL-CHO) and pyrene-1-carboxaldehyde (Py-CHO) were synthesized via Schiff’s reaction. The conjugates self-assembled into nanoparticles with pH-sensitivity to load anticancer drug doxorubicin (DOX), further coated with hyaluronic acid (HA) for tumor targeting. The mean size of nanoparticles was about 100 nm and the stability of the nanoparticles was well in aqueous solution. The nanoparticles coated with HA showed faster disassembly in acidic solution, resulting in faster drug release in the medium with pH 5.0 compared to uncoated nanoparticles. Moreover, the nanoparticles exhibited an endosomal escape function to accelerate the release of DOX in cancer cells, which led to low IC 50 s to kill breast cancer cells (4T1) and liver cancer cells (HepG2) in vitro.